text:
3351 structures 1599 species 0 interactions 30205 sequences 377 architectures
Family: Histone (PF00125)
Summary: Core histone H2A/H2B/H3/H4
Wikipedia: Histone
This is the Wikipedia entry entitled "Histone". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
Policies and quidelines
Wikipedia help contents
Wikipedia Tips
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at pfam-help@sanger.ac.uk and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Histone Edit Wikipedia article
Family proteins package and order the DNA into structural units called nucleosomes.
Schematic representation of the assembly of the core histones into the nucleosome.
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes.[1][2] Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09Â mm) of 30Â nm diameter chromatin fibers.[3]
There are five families of histones which are designated H1/H5 (linker histones), H2, H3, and H4 (core histones). The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer. The tight wrapping of DNA around histones is to a large degree a result of electrostatic attraction between the positively charged histones and negatively charged phosphate backbone of DNA.
Histones may be chemically modified through the action of enzymes to regulate gene transcription. The most common modification are the methylation of arginine or lysine residues or the acetylation of lysine. Methylation can affect how other protein such as transcription factors interact with the nucleosomes. Lysine acetylation eliminates a positive charge on lysine thereby weakening the electrostatic attraction between histone and DNA resulting in partial unwinding of the DNA making it more accessible for gene expression.
1 Classes and variants
2 Structure
3 Evolution and species distribution
4 Function
4.1 Compacting DNA strands
4.2 Chromatin regulation
5 Modification
5.1 Chemistry
5.1.1 Lysine methylation
5.1.2 Glutamine serotonylation
5.1.3 Arginine methylation
5.1.4 Arginine citrullination
5.1.5 Lysine acetylation
5.1.6 Serine/threonine/tyrosine phosphorylation
5.2 Effects on transcription
5.2.1 Actively transcribed genes
5.2.2 Repressed genes
5.2.3 Bivalent promoters
5.3 Other functions
5.3.1 DNA damage
5.3.2 DNA repair
5.3.3 Chromosome condensation
5.4 Addiction
6 Synthesis
6.1 Yeast
6.2 Metazoan
6.3 Link between cell-cycle control and synthesis
Classes and variants
Histone heterooctamer (H3,H4,H2A,H2B) + DNS fragment, Frog
Five major families of histones exist: H1/H5, H2A, H2B, H3, and H4.[2][4][5][6] Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1/H5 are known as the linker histones.
The core histones all exist as dimers, which are similar in that they all possess the histone fold domain: three alpha helices linked by two loops. It is this helical structure that allows for interaction between distinct dimers, particularly in a head-tail fashion (also called the handshake motif).[7] The resulting four distinct dimers then come together to form one octameric nucleosome core, approximately 63 Angstroms in diameter (a solenoid (DNA)-like particle). Around 146 base pairs (bp) of DNA wrap around this core particle 1.65 times in a left-handed super-helical turn to give a particle of around 100 Angstroms across.[8] The linker histone H1 binds the nucleosome at the entry and exit sites of the DNA, thus locking the DNA into place[9] and allowing the formation of higher order structure. The most basic such formation is the 10Â nm fiber or beads on a string conformation. This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of DNA separating each pair of nucleosomes (also referred to as linker DNA). Higher-order structures include the 30Â nm fiber (forming an irregular zigzag) and 100Â nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins.
Histones are subdivided into canonical replication-dependent histones that are expressed during the S-phase of the cell cycle and replication-independent histone variants, expressed during the whole cell cycle. In animals, genes encoding canonical histones are typically clustered along the chromosome, lack introns and use a stem loop structure at the 3' end instead of a polyA tail. Genes encoding histone variants are usually not clustered, have introns and their mRNAs are regulated with polyA tails. Complex multicellular organisms typically have a higher number of histone variants providing a variety of different functions. Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development.[10] Histone variants from different organisms, their classification and variant specific features can be found in "HistoneDB 2.0 - Variants" database.
The following is a list of human histone proteins:
Super family
Linker H1 H1F H1F0, H1FNT, H1FOO, H1FX
H1H1 HIST1H1A, HIST1H1B, HIST1H1C, HIST1H1D, HIST1H1E, HIST1H1T
Core H2A H2AF H2AFB1, H2AFB2, H2AFB3, H2AFJ, H2AFV, H2AFX, H2AFY, H2AFY2, H2AFZ
H2A1 HIST1H2AA, HIST1H2AB, HIST1H2AC, HIST1H2AD, HIST1H2AE, HIST1H2AG, HIST1H2AI, HIST1H2AJ, HIST1H2AK, HIST1H2AL, HIST1H2AM
H2A2 HIST2H2AA3, HIST2H2AC
H2B H2BF H2BFM, H2BFS, H2BFWT
H2B1 HIST1H2BA, HIST1H2BB, HIST1H2BC, HIST1H2BD, HIST1H2BE, HIST1H2BF, HIST1H2BG, HIST1H2BH, HIST1H2BI, HIST1H2BJ, HIST1H2BK, HIST1H2BL, HIST1H2BM, HIST1H2BN, HIST1H2BO
H2B2 HIST2H2BE
H3 H3A1 HIST1H3A, HIST1H3B, HIST1H3C, HIST1H3D, HIST1H3E, HIST1H3F, HIST1H3G, HIST1H3H, HIST1H3I, HIST1H3J
H3A2 HIST2H3C
H3A3 HIST3H3
H4 H41 HIST1H4A, HIST1H4B, HIST1H4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4G, HIST1H4H, HIST1H4I, HIST1H4J, HIST1H4K, HIST1H4L
H44 HIST4H4
Steps in nucleosome assembly
The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer, forming two nearly symmetrical halves by tertiary structure (C2 symmetry; one macromolecule is the mirror image of the other).[8] The H2A-H2B dimers and H3-H4 tetramer also show pseudodyad symmetry. The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution, all featuring a 'helix turn helix turn helix' motif (DNA-binding protein motif that recognize specific DNA sequence). They also share the feature of long 'tails' on one end of the amino acid structure - this being the location of post-translational modification (see below).[11]
Archaeal histone only contains a H3-H4 like dimeric structure made out of the same protein. Such dimeric structures can stack into a tall superhelix ("hypernucleosome") onto which DNA coils in a manner similar to nucleosome spools.[12] Only some archaeal histones have tails.[13]
The distance between the spools around which eukaryotic cells wind their DNA has been determined to range from 59 to 70 Ã….[14]
In all, histones make five types of interactions with DNA:
Salt bridges and hydrogen bonds between side chains of basic amino acids (especially lysine and arginine) and phosphate oxygens on DNA
Helix-dipoles form alpha-helixes in H2B, H3, and H4 cause a net positive charge to accumulate at the point of interaction with negatively charged phosphate groups on DNA
Hydrogen bonds between the DNA backbone and the amide group on the main chain of histone proteins
Nonpolar interactions between the histone and deoxyribose sugars on DNA
Non-specific minor groove insertions of the H3 and H2B N-terminal tails into two minor grooves each on the DNA molecule
The highly basic nature of histones, aside from facilitating DNA-histone interactions, contributes to their water solubility.
Histones are subject to post translational modification by enzymes primarily on their N-terminal tails, but also in their globular domains.[15][16] Such modifications include methylation, citrullination, acetylation, phosphorylation, SUMOylation, ubiquitination, and ADP-ribosylation. This affects their function of gene regulation.
In general, genes that are active have less bound histone, while inactive genes are highly associated with histones during interphase.[17] It also appears that the structure of histones has been evolutionarily conserved, as any deleterious mutations would be severely maladaptive. All histones have a highly positively charged N-terminus with many lysine and arginine residues.
Evolution and species distribution
Core histones are found in the nuclei of eukaryotic cells and in most Archaeal phyla, but not in bacteria.[13] However the linker histones have homologs in bacteria.[18] The unicellular algae known as dinoflagellates were previously thought to be the only eukaryotes that completely lack histones,[19] however, later studies showed that their DNA still encodes histone genes.[20] Unlike the core histones, lysine-rich linker histone (H1) proteins are found in bacteria, otherwise known as nucleoprotein HC1/HC2.[18]
It has been proposed that histone proteins are evolutionarily related to the helical part of the extended AAA+ ATPase domain, the C-domain, and to the N-terminal substrate recognition domain of Clp/Hsp100 proteins. Despite the differences in their topology, these three folds share a homologous helix-strand-helix (HSH) motif.[11]
Archaeal histones may well resemble the evolutionary precursors to eukaryotic histones.[13] Furthermore, the nucleosome (core) histones may have evolved from ribosomal proteins (RPS6/RPS15) with which they share much in common, both being short and basic proteins.[21] Histone proteins are among the most highly conserved proteins in eukaryotes, emphasizing their important role in the biology of the nucleus.[2]: 939  In contrast mature sperm cells largely use protamines to package their genomic DNA, most likely because this allows them to achieve an even higher packaging ratio.[22]
There are some variant forms in some of the major classes. They share amino acid sequence homology and core structural similarity to a specific class of major histones but also have their own feature that is distinct from the major histones. These minor histones usually carry out specific functions of the chromatin metabolism. For example, histone H3-like CENPA is associated with only the centromere region of the chromosome. Histone H2A variant H2A.Z is associated with the promoters of actively transcribed genes and also involved in the prevention of the spread of silent heterochromatin.[23] Furthermore, H2A.Z has roles in chromatin for genome stability.[24] Another H2A variant H2A.X is phosphorylated at S139 in regions around double-strand breaks and marks the region undergoing DNA repair.[25] Histone H3.3 is associated with the body of actively transcribed genes.[26]
Basic units of chromatin structure
Compacting DNA strands
Histones act as spools around which DNA winds. This enables the compaction necessary to fit the large genomes of eukaryotes inside cell nuclei: the compacted molecule is 40,000 times shorter than an unpacked molecule.
Chromatin regulation
Histone tails and their function in chromatin formation
Histones undergo posttranslational modifications that alter their interaction with DNA and nuclear proteins. The H3 and H4 histones have long tails protruding from the nucleosome, which can be covalently modified at several places. Modifications of the tail include methylation, acetylation, phosphorylation, ubiquitination, SUMOylation, citrullination, and ADP-ribosylation. The core of the histones H2A and H2B can also be modified. Combinations of modifications are thought to constitute a code, the so-called "histone code".[27][28] Histone modifications act in diverse biological processes such as gene regulation, DNA repair, chromosome condensation (mitosis) and spermatogenesis (meiosis).[29]
The common nomenclature of histone modifications is:
The name of the histone (e.g., H3)
The single-letter amino acid abbreviation (e.g., K for Lysine) and the amino acid position in the protein
The type of modification (Me: methyl, P: phosphate, Ac: acetyl, Ub: ubiquitin)
The number of modifications (only Me is known to occur in more than one copy per residue. 1, 2 or 3 is mono-, di- or tri-methylation)
So H3K4me1 denotes the monomethylation of the 4th residue (a lysine) from the start (i.e., the N-terminal) of the H3 protein.
Examples of histone modifications in transcriptional regulation
H3K4
H3K14
H2BK5
H2BK20
mono-methylation activation[30] activation[31] activation[31] activation[31][32] activation[31] activation[31]
di-methylation repression[33] repression[33] activation[32]
tri-methylation activation[34] repression[31] repression[31] activation,[32]
repression[31] activation repression[33]
acetylation activation[35] activation[34] activation[34] activation[36] activation
Schematic representation of histone modifications. Based on Rodriguez-Paredes and Esteller, Nature, 2011
A huge catalogue of histone modifications have been described, but a functional understanding of most is still lacking. Collectively, it is thought that histone modifications may underlie a histone code, whereby combinations of histone modifications have specific meanings. However, most functional data concerns individual prominent histone modifications that are biochemically amenable to detailed study.
Lysine methylation
The addition of one, two, or many methyl groups to lysine has little effect on the chemistry of the histone; methylation leaves the charge of the lysine intact and adds a minimal number of atoms so steric interactions are mostly unaffected. However, proteins containing Tudor, chromo or PHD domains, amongst others, can recognise lysine methylation with exquisite sensitivity and differentiate mono, di and tri-methyl lysine, to the extent that, for some lysines (e.g.: H4K20) mono, di and tri-methylation appear to have different meanings. Because of this, lysine methylation tends to be a very informative mark and dominates the known histone modification functions.
Glutamine serotonylation
Recently it has been shown, that the addition of a serotonin group to the position 5 glutamine of H3, happens in serotonergic cells such as neurons. This is part of the differentiation of the serotonergic cells. This post-translational modification happens in conjunction with the H3K4me3 modification. The serotonylation potentiates the binding of the general transcription factor TFIID to the TATA box.[37]
Arginine methylation
What was said above of the chemistry of lysine methylation also applies to arginine methylation, and some protein domains—e.g., Tudor domains—can be specific for methyl arginine instead of methyl lysine. Arginine is known to be mono- or di-methylated, and methylation can be symmetric or asymmetric, potentially with different meanings.
Arginine citrullination
Enzymes called peptidylarginine deiminases (PADs) hydrolyze the imine group of arginines and attach a keto group, so that there is one less positive charge on the amino acid residue. This process has been involved in the activation of gene expression by making the modified histones less tightly bound to DNA and thus making the chromatin more accessible.[38] PADs can also produce the opposite effect by removing or inhibiting mono-methylation of arginine residues on histones and thus antagonizing the positive effect arginine methylation has on transcriptional activity.[39]
Lysine acetylation
Addition of an acetyl group has a major chemical effect on lysine as it neutralises the positive charge. This reduces electrostatic attraction between the histone and the negatively charged DNA backbone, loosening the chromatin structure; highly acetylated histones form more accessible chromatin and tend to be associated with active transcription. Lysine acetylation appears to be less precise in meaning than methylation, in that histone acetyltransferases tend to act on more than one lysine; presumably this reflects the need to alter multiple lysines to have a significant effect on chromatin structure. The modification includes H3K27ac.
Serine/threonine/tyrosine phosphorylation
Addition of a negatively charged phosphate group can lead to major changes in protein structure, leading to the well-characterised role of phosphorylation in controlling protein function. It is not clear what structural implications histone phosphorylation has, but histone phosphorylation has clear functions as a post-translational modification, and binding domains such as BRCT have been characterised.
Effects on transcription
Most well-studied histone modifications are involved in control of transcription.
Actively transcribed genes
Two histone modifications are particularly associated with active transcription:
Trimethylation of H3 lysine 4 (H3K4me3)
This trimethylation occurs at the promoter of active genes[40][41][42] and is performed by the COMPASS complex.[43][44][45] Despite the conservation of this complex and histone modification from yeast to mammals, it is not entirely clear what role this modification plays. However, it is an excellent mark of active promoters and the level of this histone modification at a gene's promoter is broadly correlated with transcriptional activity of the gene. The formation of this mark is tied to transcription in a rather convoluted manner: early in transcription of a gene, RNA polymerase II undergoes a switch from initiating' to 'elongating', marked by a change in the phosphorylation states of the RNA polymerase II C terminal domain (CTD). The same enzyme that phosphorylates the CTD also phosphorylates the Rad6 complex,[46][47] which in turn adds a ubiquitin mark to H2B K123 (K120 in mammals).[48] H2BK123Ub occurs throughout transcribed regions, but this mark is required for COMPASS to trimethylate H3K4 at promoters.[49][50]
Trimethylation of H3 lysine 36 (H3K36me3)
This trimethylation occurs in the body of active genes and is deposited by the methyltransferase Set2.[51] This protein associates with elongating RNA polymerase II, and H3K36Me3 is indicative of actively transcribed genes.[52] H3K36Me3 is recognised by the Rpd3 histone deacetylase complex, which removes acetyl modifications from surrounding histones, increasing chromatin compaction and repressing spurious transcription.[53][54][55] Increased chromatin compaction prevents transcription factors from accessing DNA, and reduces the likelihood of new transcription events being initiated within the body of the gene. This process therefore helps ensure that transcription is not interrupted.
Repressed genes
Three histone modifications are particularly associated with repressed genes:
This histone modification is deposited by the polycomb complex PRC2.[56] It is a clear marker of gene repression,[57] and is likely bound by other proteins to exert a repressive function. Another polycomb complex, PRC1, can bind H3K27me3[57] and adds the histone modification H2AK119Ub which aids chromatin compaction.[58][59] Based on this data it appears that PRC1 is recruited through the action of PRC2, however, recent studies show that PRC1 is recruited to the same sites in the absence of PRC2.[60][61]
Di and tri-methylation of H3 lysine 9 (H3K9me2/3)
H3K9me2/3 is a well-characterised marker for heterochromatin, and is therefore strongly associated with gene repression. The formation of heterochromatin has been best studied in the yeast Schizosaccharomyces pombe, where it is initiated by recruitment of the RNA-induced transcriptional silencing (RITS) complex to double stranded RNAs produced from centromeric repeats.[62] RITS recruits the Clr4 histone methyltransferase which deposits H3K9me2/3.[63] This process is called histone methylation. H3K9Me2/3 serves as a binding site for the recruitment of Swi6 (heterochromatin protein 1 or HP1, another classic heterochromatin marker)[64][65] which in turn recruits further repressive activities including histone modifiers such as histone deacetylases and histone methyltransferases.[66]
This modification is tightly associated with heterochromatin,[67][68] although its functional importance remains unclear. This mark is placed by the Suv4-20h methyltransferase, which is at least in part recruited by heterochromatin protein 1.[67]
Bivalent promoters
Analysis of histone modifications in embryonic stem cells (and other stem cells) revealed many gene promoters carrying both H3K4Me3 and H3K27Me3, in other words these promoters display both activating and repressing marks simultaneously. This peculiar combination of modifications marks genes that are poised for transcription; they are not required in stem cells, but are rapidly required after differentiation into some lineages. Once the cell starts to differentiate, these bivalent promoters are resolved to either active or repressive states depending on the chosen lineage.[69]
Marking sites of DNA damage is an important function for histone modifications. It also protects DNA from getting destroyed by ultraviolet radiation of sun.
Phosphorylation of H2AX at serine 139 (γH2AX)
Phosphorylated H2AX (also known as gamma H2AX) is a marker for DNA double strand breaks,[70] and forms part of the response to DNA damage.[25][71] H2AX is phosphorylated early after detection of DNA double strand break, and forms a domain extending many kilobases either side of the damage.[70][72][73] Gamma H2AX acts as a binding site for the protein MDC1, which in turn recruits key DNA repair proteins[74] (this complex topic is well reviewed in[75]) and as such, gamma H2AX forms a vital part of the machinery that ensures genome stability.
Acetylation of H3 lysine 56 (H3K56Ac)
H3K56Acx is required for genome stability.[76][77] H3K56 is acetylated by the p300/Rtt109 complex,[78][79][80] but is rapidly deacetylated around sites of DNA damage. H3K56 acetylation is also required to stabilise stalled replication forks, preventing dangerous replication fork collapses.[81][82] Although in general mammals make far greater use of histone modifications than microorganisms, a major role of H3K56Ac in DNA replication exists only in fungi, and this has become a target for antibiotic development.[83]
H3K36me3 has the ability to recruit the MSH2-MSH6 (hMutSα) complex of the DNA mismatch repair pathway.[84] Consistently, regions of the human genome with high levels of H3K36me3 accumulate less somatic mutations due to mismatch repair activity.[85]
Chromosome condensation
Phosphorylation of H3 at serine 10 (phospho-H3S10)
The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic chromosome condensation.[86][87] Condensed chromosomes therefore stain very strongly for this mark, but H3S10 phosphorylation is also present at certain chromosome sites outside mitosis, for example in pericentric heterochromatin of cells during G2. H3S10 phosphorylation has also been linked to DNA damage caused by R-loop formation at highly transcribed sites.[88]
Phosphorylation H2B at serine 10/14 (phospho-H2BS10/14)
Phosphorylation of H2B at serine 10 (yeast) or serine 14 (mammals) is also linked to chromatin condensation, but for the very different purpose of mediating chromosome condensation during apoptosis.[89][90] This mark is not simply a late acting bystander in apoptosis as yeast carrying mutations of this residue are resistant to hydrogen peroxide-induced apoptotic cell death.
Epigenetic modifications of histone tails in specific regions of the brain are of central importance in addictions.[91][92][93] Once particular epigenetic alterations occur, they appear to be long lasting "molecular scars" that may account for the persistence of addictions.[91]
Cigarette smokers (about 15% of the US population) are usually addicted to nicotine.[94] After 7 days of nicotine treatment of mice, acetylation of both histone H3 and histone H4 was increased at the FosB promoter in the nucleus accumbens of the brain, causing 61% increase in FosB expression.[95] This would also increase expression of the splice variant Delta FosB. In the nucleus accumbens of the brain, Delta FosB functions as a "sustained molecular switch" and "master control protein" in the development of an addiction.[96][97]
About 7% of the US population is addicted to alcohol. In rats exposed to alcohol for up to 5 days, there was an increase in histone 3 lysine 9 acetylation in the pronociceptin promoter in the brain amygdala complex. This acetylation is an activating mark for pronociceptin. The nociceptin/nociceptin opioid receptor system is involved in the reinforcing or conditioning effects of alcohol.[98]
Methamphetamine addiction occurs in about 0.2% of the US population.[99] Chronic methamphetamine use causes methylation of the lysine in position 4 of histone 3 located at the promoters of the c-fos and the C-C chemokine receptor 2 (ccr2) genes, activating those genes in the nucleus accumbens (NAc).[100] c-fos is well known to be important in addiction.[101] The ccr2 gene is also important in addiction, since mutational inactivation of this gene impairs addiction.[100]
The first step of chromatin structure duplication is the synthesis of histone proteins: H1, H2A, H2B, H3, H4. These proteins are synthesized during S phase of the cell cycle. There are different mechanisms which contribute to the increase of histone synthesis.
Yeast carry one or two copies of each histone gene, which are not clustered but rather scattered throughout chromosomes. Histone gene transcription is controlled by multiple gene regulatory proteins such as transcription factors which bind to histone promoter regions. In budding yeast, the candidate gene for activation of histone gene expression is SBF. SBF is a transcription factor that is activated in late G1 phase, when it dissociates from its repressor Whi5. This occurs when Whi5 is phosphorylated by Cdc8 which is a G1/S Cdk.[102] Suppression of histone gene expression outside of S phases is dependent on Hir proteins which form inactive chromatin structure at the locus of histone genes, causing transcriptional activators to be blocked.[103][104]
Metazoan
In metazoans the increase in the rate of histone synthesis is due to the increase in processing of pre-mRNA to its mature form as well as decrease in mRNA degradation; this results in an increase of active mRNA for translation of histone proteins. The mechanism for mRNA activation has been found to be the removal of a segment of the 3' end of the mRNA strand, and is dependent on association with stem-loop binding protein (SLBP).[105] SLBP also stabilizes histone mRNAs during S phase by blocking degradation by the 3'hExo nuclease.[106] SLBP levels are controlled by cell-cycle proteins, causing SLBP to accumulate as cells enter S phase and degrade as cells leave S phase. SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ cdk2, at the end of S phase.[107] Metazoans also have multiple copies of histone genes clustered on chromosomes which are localized in structures called Cajal bodies as determined by genome-wide chromosome conformation capture analysis (4C-Seq).[108]
Link between cell-cycle control and synthesis
Nuclear protein Ataxia-Telangiectasia (NPAT), also known as nuclear protein coactivator of histone transcription, is a transcription factor which activates histone gene transcription on chromosomes 1 and 6 of human cells. NPAT is also a substrate of cyclin E-Cdk2, which is required for the transition between G1 phase and S phase. NPAT activates histone gene expression only after it has been phosphorylated by the G1/S-Cdk cyclin E-Cdk2 in early S phase.[109] This shows an important regulatory link between cell-cycle control and histone synthesis.
Histones were discovered in 1884 by Albrecht Kossel.[110] The word "histone" dates from the late 19th century and is derived from the German word "Histon", a word itself of uncertain origin, perhaps from Ancient Greek ἵστημι (hístēmi, "make stand") or ἱστός (histós, "loom").
In the early 1960s, before the types of histones were known and before histones were known to be highly conserved across taxonomically diverse organisms, James F. Bonner and his collaborators began a study of these proteins that were known to be tightly associated with the DNA in the nucleus of higher organisms.[111] Bonner and his postdoctoral fellow Ru Chih C. Huang showed that isolated chromatin would not support RNA transcription in the test tube, but if the histones were extracted from the chromatin, RNA could be transcribed from the remaining DNA.[112] Their paper became a citation classic.[113] Paul T'so and James Bonner had called together a World Congress on Histone Chemistry and Biology in 1964, in which it became clear that there was no consensus on the number of kinds of histone and that no one knew how they would compare when isolated from different organisms.[114][111] Bonner and his collaborators then developed methods to separate each type of histone, purified individual histones, compared amino acid compositions in the same histone from different organisms, and compared amino acid sequences  of the same histone from different organisms in collaboration with Emil Smith from UCLA.[115] For example, they found Histone IV sequence to be highly conserved between peas and calf thymus.[115] However, their work on the biochemical characteristics of individual histones did not reveal how the histones interacted with each other or with DNA to which they were tightly bound.[114]
Also in the 1960s, Vincent Allfrey and Alfred Mirsky had suggested, based on their analyses of histones, that acetylation and methylation of histones could provide a transcriptional control mechanism, but did not have available the kind of detailed analysis that later investigators were able to conduct to show how such regulation could be gene-specific.[116] Until the early 1990s, histones were dismissed by most as inert packing material for eukaryotic nuclear DNA, a view based in part on the models of Mark Ptashne and others, who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, as is the case in bacteria.
During the 1980s, Yahli Lorch and Roger Kornberg[117] showed that a nucleosome on a core promoter prevents the initiation of transcription in vitro, and Michael Grunstein[118] demonstrated that histones repress transcription in vivo, leading to the idea of the nucleosome as a general gene repressor. Relief from repression is believed to involve both histone modification and the action of chromatin-remodeling complexes. Vincent Allfrey and Alfred Mirsky had earlier proposed a role of histone modification in transcriptional activation,[119] regarded as a molecular manifestation of epigenetics. Michael Grunstein[120] and David Allis[121] found support for this proposal, in the importance of histone acetylation for transcription in yeast and the activity of the transcriptional activator Gcn5 as a histone acetyltransferase.
The discovery of the H5 histone appears to date back to the 1970s,[122] and it is now considered an isoform of Histone H1.[2][4][5][6]
Histone variants
Chromatin
Histone acetyltransferase
Histone deacetylases
Histone methyltransferase
Histone-modifying enzymes
Nucleosome
PRMT4 pathway
Histone H1
^ Youngson RM (2006). Collins Dictionary of Human Biology. Glasgow: HarperCollins. ISBNÂ 978-0-00-722134-9.
^ a b c d Cox M, Nelson DR, Lehninger AL (2005). Lehninger Principles of Biochemistry. San Francisco: W.H. Freeman. ISBNÂ 978-0-7167-4339-2.
^ Redon C, Pilch D, Rogakou E, Sedelnikova O, Newrock K, Bonner W (April 2002). "Histone H2A variants H2AX and H2AZ". Current Opinion in Genetics & Development. 12 (2): 162–9. doi:10.1016/S0959-437X(02)00282-4. PMID 11893489.
^ a b "Histone Variants Database 2.0". National Center for Biotechnology Information. Retrieved 13 January 2017.
^ a b Bhasin M, Reinherz EL, Reche PA (2006). "Recognition and classification of histones using support vector machine" (PDF). Journal of Computational Biology. 13 (1): 102–12. doi:10.1089/cmb.2006.13.102. PMID 16472024.
^ a b Hartl DL, Freifelder D, Snyder LA (1988). Basic Genetics. Boston: Jones and Bartlett Publishers. ISBNÂ 978-0-86720-090-4.
^ Mariño-Ramírez L, Kann MG, Shoemaker BA, Landsman D (October 2005). "Histone structure and nucleosome stability". Expert Review of Proteomics. 2 (5): 719–29. doi:10.1586/14789450.2.5.719. PMC 1831843. PMID 16209651.
^ a b Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (September 1997). "Crystal structure of the nucleosome core particle at 2.8 A resolution". Nature. 389 (6648): 251–60. Bibcode:1997Natur.389..251L. doi:10.1038/38444. PMID 9305837. S2CID 4328827. PDB: 1AOI
^ Farkas D (1996). DNA simplified: the hitchhiker's guide to DNA. Washington, D.C: AACC Press. ISBNÂ 978-0-915274-84-0.
^ Jang CW, Shibata Y, Starmer J, Yee D, Magnuson T (July 2015). "Histone H3.3 maintains genome integrity during mammalian development". Genes & Development. 29 (13): 1377–92. doi:10.1101/gad.264150.115. PMC 4511213. PMID 26159997.
^ a b Alva V, Ammelburg M, Söding J, Lupas AN (March 2007). "On the origin of the histone fold". BMC Structural Biology. 7: 17. doi:10.1186/1472-6807-7-17. PMC 1847821. PMID 17391511.
^ Mattiroli F, Bhattacharyya S, Dyer PN, White AE, Sandman K, Burkhart BW, et al. (August 2017). "Structure of histone-based chromatin in Archaea". Science. 357 (6351): 609–612. Bibcode:2017Sci...357..609M. doi:10.1126/science.aaj1849. PMC 5747315. PMID 28798133.
^ a b c Henneman B, van Emmerik C, van Ingen H, Dame RT (September 2018). "Structure and function of archaeal histones". PLOS Genetics. 14 (9): e1007582. Bibcode:2018BpJ...114..446H. doi:10.1371/journal.pgen.1007582. PMCÂ 6136690. PMIDÂ 30212449.
^ Ward R, Bowman A, El-Mkami H, Owen-Hughes T, Norman DG (February 2009). "Long distance PELDOR measurements on the histone core particle". Journal of the American Chemical Society. 131 (4): 1348–9. doi:10.1021/ja807918f. PMC 3501648. PMID 19138067.
^ Mersfelder EL, Parthun MR (19 May 2006). "The tale beyond the tail: histone core domain modifications and the regulation of chromatin structure". Nucleic Acids Research. 34 (9): 2653–62. doi:10.1093/nar/gkl338. PMC 1464108. PMID 16714444.
^ Tropberger P, Schneider R (June 2013). "Scratching the (lateral) surface of chromatin regulation by histone modifications". Nature Structural & Molecular Biology. 20 (6): 657–61. doi:10.1038/nsmb.2581. PMID 23739170. S2CID 2956823.
^ Allison LA (2012). Fundamental Molecular Biology (Second ed.). United States of America: John Wiley & Sons. p. 102. ISBN 9781118059814.
^ a b Kasinsky HE, Lewis JD, Dacks JB, Ausió J (January 2001). "Origin of H1 linker histones". FASEB Journal. 15 (1): 34–42. doi:10.1096/fj.00-0237rev. PMID 11149891. S2CID 10089116.
^ Rizzo PJ (August 2003). "Those amazing dinoflagellate chromosomes". Cell Research. 13 (4): 215–7. doi:10.1038/sj.cr.7290166. PMID 12974611.
^ Talbert PB, Henikoff S (December 2012). "Chromatin: packaging without nucleosomes". Current Biology. 22 (24): R1040-3. doi:10.1016/j.cub.2012.10.052. PMIDÂ 23257187.
^ Bozorgmehr JH (February 2020). "The origin of chromosomal histones in a 30S ribosomal protein". Gene. 726: 144155. doi:10.1016/j.gene.2019.144155. PMIDÂ 31629821.
^ Clarke HJ (1992). "Nuclear and chromatin composition of mammalian gametes and early embryos". Biochemistry and Cell Biology. 70 (10–11): 856–66. doi:10.1139/o92-134. PMID 1297351.
^ Guillemette B, Bataille AR, Gévry N, Adam M, Blanchette M, Robert F, Gaudreau L (December 2005). "Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning". PLOS Biology. 3 (12): e384. doi:10.1371/journal.pbio.0030384. PMC 1275524. PMID 16248679.
^ Billon P, Côté J (October 2011). "Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance". Biochim Biophys Acta. 1819 (3–4): 290–302. doi:10.1016/j.bbagrm.2011.10.004. PMID 22027408.
^ a b Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000). "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage". Current Biology. 10 (15): 886–95. doi:10.1016/S0960-9822(00)00610-2. PMID 10959836.
^ Ahmad K, Henikoff S (June 2002). "The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly". Molecular Cell. 9 (6): 1191–200. doi:10.1016/S1097-2765(02)00542-7. PMID 12086617.
^ Strahl BD, Allis CD (January 2000). "The language of covalent histone modifications". Nature. 403 (6765): 41–5. Bibcode:2000Natur.403...41S. doi:10.1038/47412. PMID 10638745. S2CID 4418993.
^ Jenuwein T, Allis CD (August 2001). "Translating the histone code" (PDF). Science. 293 (5532): 1074–80. CiteSeerX 10.1.1.453.900. doi:10.1126/science.1063127. PMID 11498575. S2CID 1883924.
^ Song N, Liu J, An S, Nishino T, Hishikawa Y, Koji T (August 2011). "Immunohistochemical Analysis of Histone H3 Modifications in Germ Cells during Mouse Spermatogenesis". Acta Histochemica et Cytochemica. 44 (4): 183–90. doi:10.1267/ahc.11027. PMC 3168764. PMID 21927517.
^ Benevolenskaya EV (August 2007). "Histone H3K4 demethylases are essential in development and differentiation". Biochemistry and Cell Biology. 85 (4): 435–43. doi:10.1139/o07-057. PMID 17713579.
^ a b c d e f g h Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. (May 2007). "High-resolution profiling of histone methylations in the human genome". Cell. 129 (4): 823–37. doi:10.1016/j.cell.2007.05.009. PMID 17512414.
^ a b c Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, et al. (April 2008). "DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells". Molecular and Cellular Biology. 28 (8): 2825–39. doi:10.1128/MCB.02076-07. PMC 2293113. PMID 18285465.
^ a b c Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ (March 2009). "Determination of enriched histone modifications in non-genic portions of the human genome". BMC Genomics. 10: 143. doi:10.1186/1471-2164-10-143. PMCÂ 2667539. PMIDÂ 19335899.
^ a b c Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, et al. (June 2007). "The landscape of histone modifications across 1% of the human genome in five human cell lines". Genome Research. 17 (6): 691–707. doi:10.1101/gr.5704207. PMC 1891331. PMID 17567990.
^ Guillemette B, Drogaris P, Lin HH, Armstrong H, Hiragami-Hamada K, Imhof A, et al. (March 2011). "H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation". PLOS Genetics. 7 (3): e1001354. doi:10.1371/journal.pgen.1001354. PMC 3069113. PMID 21483810.
^ Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. (December 2010). "Histone H3K27ac separates active from poised enhancers and predicts developmental state". Proceedings of the National Academy of Sciences of the United States of America. 107 (50): 21931–6. doi:10.1073/pnas.1016071107. PMC 3003124. PMID 21106759.
^ Farrelly LA, Thompson RE, Zhao S, Lepack AE, Lyu Y, Bhanu NV, et al. (March 2019). "Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3". Nature. 567 (7749): 535–539. Bibcode:2019Natur.567..535F. doi:10.1038/s41586-019-1024-7. PMC 6557285. PMID 30867594.
^ Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, et al. (March 2014). "Citrullination regulates pluripotency and histone H1 binding to chromatin". Nature. 507 (7490): 104–8. Bibcode:2014Natur.507..104C. doi:10.1038/nature12942. PMC 4843970. PMID 24463520.
^ Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, et al. (September 2004). "Histone deimination antagonizes arginine methylation". Cell. 118 (5): 545–53. doi:10.1016/j.cell.2004.08.020. PMID 15339660.
^ Krogan NJ, Dover J, Wood A, Schneider J, Heidt J, Boateng MA, et al. (March 2003). "The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation". Molecular Cell. 11 (3): 721–9. doi:10.1016/S1097-2765(03)00091-1. PMID 12667454.
^ Ng HH, Robert F, Young RA, Struhl K (March 2003). "Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity". Molecular Cell. 11 (3): 709–19. doi:10.1016/S1097-2765(03)00092-3. PMID 12667453.
^ Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, et al. (January 2005). "Genomic maps and comparative analysis of histone modifications in human and mouse". Cell. 120 (2): 169–81. doi:10.1016/j.cell.2005.01.001. PMID 15680324.
^ Krogan NJ, Dover J, Khorrami S, Greenblatt JF, Schneider J, Johnston M, Shilatifard A (March 2002). "COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression". The Journal of Biological Chemistry. 277 (13): 10753–5. doi:10.1074/jbc.C200023200. PMID 11805083.
^ Roguev A, Schaft D, Shevchenko A, Pijnappel WW, Wilm M, Aasland R, Stewart AF (December 2001). "The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4". The EMBO Journal. 20 (24): 7137–48. doi:10.1093/emboj/20.24.7137. PMC 125774. PMID 11742990.
^ Nagy PL, Griesenbeck J, Kornberg RD, Cleary ML (January 2002). "A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3". Proceedings of the National Academy of Sciences of the United States of America. 99 (1): 90–4. Bibcode:2002PNAS...99...90N. doi:10.1073/pnas.221596698. PMC 117519. PMID 11752412.
^ Wood A, Schneider J, Dover J, Johnston M, Shilatifard A (November 2005). "The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS". Molecular Cell. 20 (4): 589–99. doi:10.1016/j.molcel.2005.09.010. PMID 16307922.
^ Sarcevic B, Mawson A, Baker RT, Sutherland RL (April 2002). "Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation". The EMBO Journal. 21 (8): 2009–18. doi:10.1093/emboj/21.8.2009. PMC 125963. PMID 11953320.
^ Robzyk K, Recht J, Osley MA (January 2000). "Rad6-dependent ubiquitination of histone H2B in yeast". Science. 287 (5452): 501–4. Bibcode:2000Sci...287..501R. doi:10.1126/science.287.5452.501. PMID 10642555.
^ Sun ZW, Allis CD (July 2002). "Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast". Nature. 418 (6893): 104–8. Bibcode:2002Natur.418..104S. doi:10.1038/nature00883. PMID 12077605. S2CID 4338471.
^ Dover J, Schneider J, Tawiah-Boateng MA, Wood A, Dean K, Johnston M, Shilatifard A (August 2002). "Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6". The Journal of Biological Chemistry. 277 (32): 28368–71. doi:10.1074/jbc.C200348200. PMID 12070136.
^ Strahl BD, Grant PA, Briggs SD, Sun ZW, Bone JR, Caldwell JA, et al. (March 2002). "Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression". Molecular and Cellular Biology. 22 (5): 1298–306. doi:10.1128/MCB.22.5.1298-1306.2002. PMC 134702. PMID 11839797.
^ Li J, Moazed D, Gygi SP (December 2002). "Association of the histone methyltransferase Set2 with RNA polymerase II plays a role in transcription elongation". The Journal of Biological Chemistry. 277 (51): 49383–8. doi:10.1074/jbc.M209294200. PMID 12381723.
^ Carrozza MJ, Li B, Florens L, Suganuma T, Swanson SK, Lee KK, et al. (November 2005). "Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription". Cell. 123 (4): 581–92. doi:10.1016/j.cell.2005.10.023. PMID 16286007.
^ Keogh MC, Kurdistani SK, Morris SA, Ahn SH, Podolny V, Collins SR, et al. (November 2005). "Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex". Cell. 123 (4): 593–605. doi:10.1016/j.cell.2005.10.025. PMID 16286008.
^ Joshi AA, Struhl K (December 2005). "Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation". Molecular Cell. 20 (6): 971–8. doi:10.1016/j.molcel.2005.11.021. PMID 16364921.
^ Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D (November 2002). "Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein". Genes & Development. 16 (22): 2893–905. doi:10.1101/gad.1035902. PMC 187479. PMID 12435631.
^ a b Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, et al. (November 2002). "Role of histone H3 lysine 27 methylation in Polycomb-group silencing". Science. 298 (5595): 1039–43. Bibcode:2002Sci...298.1039C. doi:10.1126/science.1076997. PMID 12351676. S2CID 6265267.
^ de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, et al. (November 2004). "Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation". Developmental Cell. 7 (5): 663–76. doi:10.1016/j.devcel.2004.10.005. PMID 15525528.
^ Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, Zhang Y (October 2004). "Role of histone H2A ubiquitination in Polycomb silencing". Nature. 431 (7010): 873–8. Bibcode:2004Natur.431..873W. doi:10.1038/nature02985. hdl:10261/73732. PMID 15386022. S2CID 4344378.
^ Tavares L, Dimitrova E, Oxley D, Webster J, Poot R, Demmers J, et al. (February 2012). "RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3". Cell. 148 (4): 664–78. doi:10.1016/j.cell.2011.12.029. PMC 3281992. PMID 22325148.
^ Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, et al. (February 2012). "PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes". Molecular Cell. 45 (3): 344–56. doi:10.1016/j.molcel.2012.01.002. PMC 3293217. PMID 22325352.
^ Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D (January 2004). "RNAi-mediated targeting of heterochromatin by the RITS complex". Science. 303 (5658): 672–6. Bibcode:2004Sci...303..672V. doi:10.1126/science.1093686. PMC 3244756. PMID 14704433.
^ Rea S, Eisenhaber F, O'Carroll D, Strahl BD, Sun ZW, Schmid M, et al. (August 2000). "Regulation of chromatin structure by site-specific histone H3 methyltransferases". Nature. 406 (6796): 593–9. Bibcode:2000Natur.406..593R. doi:10.1038/35020506. PMID 10949293. S2CID 205008015.
^ Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (March 2001). "Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain". Nature. 410 (6824): 120–4. Bibcode:2001Natur.410..120B. doi:10.1038/35065138. PMID 11242054. S2CID 4334447.
^ Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T (March 2001). "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins". Nature. 410 (6824): 116–20. Bibcode:2001Natur.410..116L. doi:10.1038/35065132. PMID 11242053. S2CID 4331863.
^ Bajpai G, Jain I, Inamdar MM, Das D, Padinhateeri R (January 2017). "Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure". PLOS Computational Biology. 13 (1): e1005365. Bibcode:2017PLSCB..13E5365B. doi:10.1371/journal.pcbi.1005365. PMCÂ 5305278. PMIDÂ 28135276.
^ a b Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, et al. (June 2004). "A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin". Genes & Development. 18 (11): 1251–62. doi:10.1101/gad.300704. PMC 420351. PMID 15145825.
^ Kourmouli N, Jeppesen P, Mahadevhaiah S, Burgoyne P, Wu R, Gilbert DM, et al. (May 2004). "Heterochromatin and tri-methylated lysine 20 of histone H4 in animals". Journal of Cell Science. 117 (Pt 12): 2491–501. doi:10.1242/jcs.01238. PMID 15128874.
^ Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, et al. (April 2006). "A bivalent chromatin structure marks key developmental genes in embryonic stem cells". Cell. 125 (2): 315–26. doi:10.1016/j.cell.2006.02.041. PMID 16630819.
^ a b Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (March 1998). "DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139". The Journal of Biological Chemistry. 273 (10): 5858–68. doi:10.1074/jbc.273.10.5858. PMID 9488723.
^ Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, et al. (May 2002). "Genomic instability in mice lacking histone H2AX". Science. 296 (5569): 922–7. Bibcode:2002Sci...296..922C. doi:10.1126/science.1069398. PMC 4721576. PMID 11934988.
^ Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM, Petrini JH, et al. (October 2004). "Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break". Current Biology. 14 (19): 1703–11. doi:10.1016/j.cub.2004.09.047. PMC 4493763. PMID 15458641.
^ Rogakou EP, Boon C, Redon C, Bonner WM (September 1999). "Megabase chromatin domains involved in DNA double-strand breaks in vivo". The Journal of Cell Biology. 146 (5): 905–16. doi:10.1083/jcb.146.5.905. PMC 2169482. PMID 10477747.
^ Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ (February 2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". Nature. 421 (6926): 961–6. Bibcode:2003Natur.421..961S. doi:10.1038/nature01446. PMID 12607005. S2CID 4410773.
^ Bekker-Jensen S, Mailand N (December 2010). "Assembly and function of DNA double-strand break repair foci in mammalian cells". DNA Repair. 9 (12): 1219–28. doi:10.1016/j.dnarep.2010.09.010. PMID 21035408.
^ Ozdemir A, Spicuglia S, Lasonder E, Vermeulen M, Campsteijn C, Stunnenberg HG, Logie C (July 2005). "Characterization of lysine 56 of histone H3 as an acetylation site in Saccharomyces cerevisiae". The Journal of Biological Chemistry. 280 (28): 25949–52. doi:10.1074/jbc.C500181200. PMID 15888442.
^ Masumoto H, Hawke D, Kobayashi R, Verreault A (July 2005). "A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response". Nature. 436 (7048): 294–8. Bibcode:2005Natur.436..294M. doi:10.1038/nature03714. PMID 16015338. S2CID 4414433.
^ Driscoll R, Hudson A, Jackson SP (February 2007). "Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56". Science. 315 (5812): 649–52. Bibcode:2007Sci...315..649D. doi:10.1126/science.1135862. PMC 3334813. PMID 17272722.
^ Han J, Zhou H, Horazdovsky B, Zhang K, Xu RM, Zhang Z (February 2007). "Rtt109 acetylates histone H3 lysine 56 and functions in DNA replication". Science. 315 (5812): 653–5. Bibcode:2007Sci...315..653H. doi:10.1126/science.1133234. PMID 17272723. S2CID 19056605.
^ Das C, Lucia MS, Hansen KC, Tyler JK (May 2009). "CBP/p300-mediated acetylation of histone H3 on lysine 56". Nature. 459 (7243): 113–7. Bibcode:2009Natur.459..113D. doi:10.1038/nature07861. PMC 2756583. PMID 19270680.
^ Han J, Zhou H, Li Z, Xu RM, Zhang Z (September 2007). "Acetylation of lysine 56 of histone H3 catalyzed by RTT109 and regulated by ASF1 is required for replisome integrity". The Journal of Biological Chemistry. 282 (39): 28587–96. doi:10.1074/jbc.M702496200. PMID 17690098.
^ Wurtele H, Kaiser GS, Bacal J, St-Hilaire E, Lee EH, Tsao S, et al. (January 2012). "Histone H3 lysine 56 acetylation and the response to DNA replication fork damage". Molecular and Cellular Biology. 32 (1): 154–72. doi:10.1128/MCB.05415-11. PMC 3255698. PMID 22025679.
^ Wurtele H, Tsao S, Lépine G, Mullick A, Tremblay J, Drogaris P, et al. (July 2010). "Modulation of histone H3 lysine 56 acetylation as an antifungal therapeutic strategy". Nature Medicine. 16 (7): 774–80. doi:10.1038/nm.2175. PMC 4108442. PMID 20601951.
^ Li F, Mao G, Tong D, Huang J, Gu L, Yang W, Li GM (April 2013). "The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα". Cell. 153 (3): 590–600. doi:10.1016/j.cell.2013.03.025. PMC 3641580. PMID 23622243.
^ Supek F, Lehner B (July 2017). "Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes". Cell. 170 (3): 534–547.e23. doi:10.1016/j.cell.2017.07.003. hdl:10230/35343. PMID 28753428.
^ Wilkins BJ, Rall NA, Ostwal Y, Kruitwagen T, Hiragami-Hamada K, Winkler M, et al. (January 2014). "A cascade of histone modifications induces chromatin condensation in mitosis". Science. 343 (6166): 77–80. Bibcode:2014Sci...343...77W. doi:10.1126/science.1244508. hdl:11858/00-001M-0000-0015-11C0-5. PMID 24385627. S2CID 7698266.
^ Johansen KM, Johansen J (2006). "Regulation of chromatin structure by histone H3S10 phosphorylation". Chromosome Research. 14 (4): 393–404. doi:10.1007/s10577-006-1063-4. PMID 16821135. S2CID 8556959.
^ Castellano-Pozo M, Santos-Pereira JM, Rondón AG, Barroso S, Andújar E, Pérez-Alegre M, et al. (November 2013). "R loops are linked to histone H3 S10 phosphorylation and chromatin condensation". Molecular Cell. 52 (4): 583–90. doi:10.1016/j.molcel.2013.10.006. PMID 24211264.
^ Cheung WL, Ajiro K, Samejima K, Kloc M, Cheung P, Mizzen CA, et al. (May 2003). "Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase". Cell. 113 (4): 507–17. doi:10.1016/s0092-8674(03)00355-6. PMID 12757711.
^ Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD (January 2005). "Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae". Cell. 120 (1): 25–36. doi:10.1016/j.cell.2004.11.016. PMID 15652479.
^ a b Robison AJ, Nestler EJ (October 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews. Neuroscience. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194.
^ Hitchcock LN, Lattal KM (2014). "Histone-mediated epigenetics in addiction". Epigenetics and Neuroplasticity—Evidence and Debate. Prog Mol Biol Transl Sci. Progress in Molecular Biology and Translational Science. Vol. 128. pp. 51–87. doi:10.1016/B978-0-12-800977-2.00003-6. ISBN 9780128009772. PMC 5914502. PMID 25410541.
^ McQuown SC, Wood MA (April 2010). "Epigenetic regulation in substance use disorders". Current Psychiatry Reports. 12 (2): 145–53. doi:10.1007/s11920-010-0099-5. PMC 2847696. PMID 20425300.
^ "Is nicotine addictive?".
^ Levine A, Huang Y, Drisaldi B, Griffin EA, Pollak DD, Xu S, et al. (November 2011). "Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine". Science Translational Medicine. 3 (107): 107ra109. doi:10.1126/scitranslmed.3003062. PMC 4042673. PMID 22049069.
^ Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". The American Journal of Drug and Alcohol Abuse. 40 (6): 428–37. doi:10.3109/00952990.2014.933840. PMID 25083822. S2CID 19157711.
^ Nestler EJ, Barrot M, Self DW (September 2001). "DeltaFosB: a sustained molecular switch for addiction". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11042–6. Bibcode:2001PNAS...9811042N. doi:10.1073/pnas.191352698. PMC 58680. PMID 11572966.
^ D'Addario C, Caputi FF, Ekström TJ, Di Benedetto M, Maccarrone M, Romualdi P, Candeletti S (February 2013). "Ethanol induces epigenetic modulation of prodynorphin and pronociceptin gene expression in the rat amygdala complex". Journal of Molecular Neuroscience. 49 (2): 312–9. doi:10.1007/s12031-012-9829-y. PMID 22684622. S2CID 14013417.
^ "What is the scope of methamphetamine abuse in the United States?".
^ a b Godino A, Jayanthi S, Cadet JL (2015). "Epigenetic landscape of amphetamine and methamphetamine addiction in rodents". Epigenetics. 10 (7): 574–80. doi:10.1080/15592294.2015.1055441. PMC 4622560. PMID 26023847.
^ Cruz FC, Javier Rubio F, Hope BT (December 2015). "Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction". Brain Research. 1628 (Pt A): 157–73. doi:10.1016/j.brainres.2014.11.005. PMC 4427550. PMID 25446457.
^ de Bruin RA, McDonald WH, Kalashnikova TI, Yates J, Wittenberg C (June 2004). "Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5". Cell. 117 (7): 887–98. doi:10.1016/j.cell.2004.05.025. PMID 15210110.
^ Xu H, Kim UJ, Schuster T, Grunstein M (November 1992). "Identification of a new set of cell cycle-regulatory genes that regulate S-phase transcription of histone genes in Saccharomyces cerevisiae". Molecular and Cellular Biology. 12 (11): 5249–59. doi:10.1128/mcb.12.11.5249. PMC 360458. PMID 1406694.
^ Dimova D, Nackerdien Z, Furgeson S, Eguchi S, Osley MA (July 1999). "A role for transcriptional repressors in targeting the yeast Swi/Snf complex". Molecular Cell. 4 (1): 75–83. doi:10.1016/S1097-2765(00)80189-6. PMID 10445029.
^ Dominski Z, Erkmann JA, Yang X, Sà nchez R, Marzluff WF (January 2002). "A novel zinc finger protein is associated with U7 snRNP and interacts with the stem-loop binding protein in the histone pre-mRNP to stimulate 3'-end processing". Genes & Development. 16 (1): 58–71. doi:10.1101/gad.932302. PMC 155312. PMID 11782445.
^ Dominski Z, Yang XC, Kaygun H, Dadlez M, Marzluff WF (August 2003). "A 3' exonuclease that specifically interacts with the 3' end of histone mRNA". Molecular Cell. 12 (2): 295–305. doi:10.1016/S1097-2765(03)00278-8. PMID 14536070.
^ Zheng L, Dominski Z, Yang XC, Elms P, Raska CS, Borchers CH, Marzluff WF (March 2003). "Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase". Molecular and Cellular Biology. 23 (5): 1590–601. doi:10.1128/MCB.23.5.1590-1601.2003. PMC 151715. PMID 12588979.
^ Wang Q, Sawyer IA, Sung MH, Sturgill D, Shevtsov SP, Pegoraro G, et al. (March 2016). "Cajal bodies are linked to genome conformation". Nature Communications. 7: 10966. Bibcode:2016NatCo...710966W. doi:10.1038/ncomms10966. PMC 4802181. PMID 26997247.
^ Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E (September 2000). "NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription". Genes & Development. 14 (18): 2283–97. doi:10.1101/GAD.827700. PMC 316937. PMID 10995386.
^ Luck JM (1965). "Histone Chemistry: the Pioneers". In Bonner J, Ts'o P (eds.). The Nucleohistones. San Francisco, London, and Amsterdam: Holden-Day, Inc.
^ a b Bonner J (1994). "Chapters from my life". Annual Review of Plant Physiology and Plant Molecular Biology. 45: 1–23. doi:10.1146/annurev.pp.45.060194.000245.
^ Huang RC, Bonner J (July 1962). "Histone, a suppressor of chromosomal RNA synthesis". Proceedings of the National Academy of Sciences of the United States of America. 48 (7): 1216–22. Bibcode:1962PNAS...48.1216H. doi:10.1073/pnas.48.7.1216. PMC 220935. PMID 14036409.
^ "Huang R C & Bonner J. Histone, a suppressor of chromosomal RNA synthesis. Proc. Nat. Acad. Sci. US 48:1216-22, 1962" (PDF). Citation Classics (12): 79. 20 March 1978.
^ a b James Bonner and Paul T'so (1965) The Nucleohistones. Holden-Day Inc, San Francisco, London, Amsterdam.
^ a b DeLange RJ, Fambrough DM, Smith EL, Bonner J (October 1969). "Calf and pea histone IV. 3. Complete amino acid sequence of pea seedling histone IV; comparison with the homologous calf thymus histone". The Journal of Biological Chemistry. 244 (20): 5669–79. doi:10.1016/S0021-9258(18)63612-9. PMID 5388597.
^ Allfrey VG, Faulkner R, Mirsky AE (May 1964). "Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis". Proceedings of the National Academy of Sciences of the United States of America. 51 (5): 786–94. Bibcode:1964PNAS...51..786A. doi:10.1073/pnas.51.5.786. PMC 300163. PMID 14172992.
^ Lorch Y, LaPointe JW, Kornberg RD (April 1987). "Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones". Cell. 49 (2): 203–10. doi:10.1016/0092-8674(87)90561-7. PMID 3568125. S2CID 21270171.
^ Kayne PS, Kim UJ, Han M, Mullen JR, Yoshizaki F, Grunstein M (October 1988). "Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast". Cell. 55 (1): 27–39. doi:10.1016/0092-8674(88)90006-2. PMID 3048701. S2CID 7994350.
^ Pogo BG, Allfrey VG, Mirsky AE (April 1966). "RNA synthesis and histone acetylation during the course of gene activation in lymphocytes". Proceedings of the National Academy of Sciences of the United States of America. 55 (4): 805–12. Bibcode:1966PNAS...55..805P. doi:10.1073/pnas.55.4.805. PMC 224233. PMID 5219687.
^ Durrin LK, Mann RK, Kayne PS, Grunstein M (June 1991). "Yeast histone H4 N-terminal sequence is required for promoter activation in vivo". Cell. 65 (6): 1023–31. doi:10.1016/0092-8674(91)90554-c. PMID 2044150. S2CID 28169631.
^ Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD (March 1996). "Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation". Cell. 84 (6): 843–51. doi:10.1016/s0092-8674(00)81063-6. PMID 8601308.
^ Aviles FJ, Chapman GE, Kneale GG, Crane-Robinson C, Bradbury EM (August 1978). "The conformation of histone H5. Isolation and characterisation of the globular segment". European Journal of Biochemistry. 88 (2): 363–71. doi:10.1111/j.1432-1033.1978.tb12457.x. PMID 689022.
Look up histone in Wiktionary, the free dictionary.
HistoneDB 2.0 - Database of histones and variants at NCBI
Chromatin, Histones & Cathepsin; PMAP The Proteolysis Map-animation
Cytogenetics: chromosomes
Ploidy
Genetic material/Genome
Euchromatin
Heterochromatin
Chromatid
Nuclear organization
Autosome/Sex chromosome (or allosome or heterosome)
Macrochromosome/Microchromosome
Circular chromosome/Linear chromosome
Extra chromosome (or accessory chromosome)
Supernumerary chromosome
A chromosome/B chromosome
Lampbrush chromosome
Polytene chromosome
Dinoflagellate chromosomes
Homologous chromosome
Isochromosome
Satellite chromosome
Centromere position
Metacentric
Submetacentric
Telocentric
Acrocentric
Holocentric
Centromere number
Acentric
Monocentric
Dicentric
and evolution
Chromosomal inversion
Chromosomal translocation
Numerical alterations
Aneuploidy
Euploidy
Polyploidy
Paleopolyploidy
Polyploidization
Telomere: Telomere-binding protein (TINF2)
Protamine
H2A
Extrachromosomal DNA
List of organisms by chromosome count
List of sequenced genomes
International System for Human Cytogenetic Nomenclature
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
Core histone H2A/H2B/H3/H4 Provide feedback
No Pfam abstract.
Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ; , Nature 1997;389:251-260.: Crystal structure of the nucleosome core particle at 2.8 A resolution. PUBMED:9305837 EPMC:9305837
SCOOP: Bromo_TP CBFD_NFYB_HMF CENP-S CENP-T_C CENP-W CIS_TMP PAF TAF TAFII28 TFIID-18kDa TFIID-31kDa TFIID_20kDa YscO-like
Similarity to PfamA using HHSearch: CBFD_NFYB_HMF TFIID-31kDa TAF TFIID_20kDa CENP-T_C CENP-S
HOMSTRAD: histone
PRINTS: PR00620 PR00621 PR00622 PR00623
PROSITE: PDOC00045 PDOC00046 PDOC00287 PDOC00308
SCOP: 1hio
InterPro entry IPR007125
Five major families of histones exist: H1/H5, H2A, H2B, H3, and H4 [ PUBMED:16472024 ]. Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1 and H5 are known as the linker histones. The core histones together with some other DNA binding proteins form a superfamily defined by a common fold and distant sequence similarities [ PUBMED:7651829 , PUBMED:9016552 ]. Some proteins contain local homology domains related to the histone fold [ PUBMED:9305837 ].
This entry represents a domain found in histones H2A, H2B and H3. This domain can also be found in transcription factors, such as OsNF-YC2 from rice [ PUBMED:26542958 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function DNA binding (GO:0003677)
This family is a member of clan Histone (CL0012), which has the following description:
Members of this clan all possess a histone fold. Generally proteins in this clan are DNA binding.
The clan contains the following 17 members:
Bromo_TP Bromo_TP_like CBFD_NFYB_HMF CENP-S CENP-T_C CENP-W CENP-X DUF1931 Histone PAF TAF TAF4 TAFII28 TFIID-18kDa TFIID-31kDa TFIID_20kDa TFIID_30kDa
HTML View
PP/heatmap 1
Seed source: Prosite
Previous IDs: histone;
Author: Bateman A , Sonnhammer ELL
Number in seed: 27
Number in full: 30205
Family (HMM) version: 27
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Histone domain has been found. There are 3351 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
A0A087WP11 View 3D Structure Click here
A0A0G2JXE0 View 3D Structure Click here
A0A0G2JXI9 View 3D Structure Click here
A0A0G2K0N8 View 3D Structure Click here
A0A0G2K0W2 View 3D Structure Click here
A0A0G2K5X7 View 3D Structure Click here
A0A0G2K7R1 View 3D Structure Click here
A0A0G2K9I5 View 3D Structure Click here
A0A0N7KF87 View 3D Structure Click here
A0A0P0VIN6 View 3D Structure Click here
A0A0P0WN72 View 3D Structure Click here
A0A0P0WTA4 View 3D Structure Click here
A0A0P0XRT5 View 3D Structure Click here
A0A0R0EJ77 View 3D Structure Click here
A0A0R0F3E0 View 3D Structure Click here
A0A0R0FIN9 View 3D Structure Click here
A0A0R0FTE6 View 3D Structure Click here
A0A0R0GW87 View 3D Structure Click here
A0A0R0H449 View 3D Structure Click here
A0A0R0H6V3 View 3D Structure Click here
A0A0R0HEQ3 View 3D Structure Click here
A0A0R0HLG7 View 3D Structure Click here
A0A0R0HPZ5 View 3D Structure Click here
A0A0R0KK01 View 3D Structure Click here
A0A0R0KKD0 View 3D Structure Click here
A0A0R0KNL8 View 3D Structure Click here
A0A0R4IPN8 View 3D Structure Click here
A0A0R4J2W1 View 3D Structure Click here
A0A0R4J661 View 3D Structure Click here
A0A140LG23 View 3D Structure Click here
A0A140LGS2 View 3D Structure Click here
A0A1D6ELS0 View 3D Structure Click here
A0A1D6F342 View 3D Structure Click here
A0A1D6FJ21 View 3D Structure Click here
A0A1D6FVI7 View 3D Structure Click here
A0A1D6J6J4 View 3D Structure Click here
A0A1D6JDH2 View 3D Structure Click here
Showing 40 matches


text:
Celtic Could Achieve Much Moore With Liam At The Back
Celtic have reasserted themselves atop the Scottish Premiership in recent weeks, hammering their closest rivals Aberdeen before making history with their win over St. Johnstone, which sealed a record-breaking 63rd domestic consecutive game without defeat.
They also put forth an excellent effort in Champions League action, competing with German giants Bayern Munich on their own turf before losing 2-1. The performance deserved more, suggesting the Scottish champions have what it takes to secure third place in their group and Europa League football after Christmas.
Brendan Rodgers, however, appears determined not to allow the side to rest on their laurels. In pursuit of a seventh straight title and a concerted push on the continent, he has reportedly begun the process of identifying players who can strengthen his hand in January, with Liam Moore the latest to be linked.
Celtic have suffered injuries to two of their key centre-backs in Jozo Šimunović and Erik Sviatchenko this season, something that has only been compounded by the recent switch to a back three. Consequently, it makes sense for them to target central defensive reinforcements in the upcoming transfer window.
Moore would fit the bill from a purely positional sense, but why else should Rodgers look to him as a solution? Here we break down the player's qualities and consider whether he'd be a suitable signing.
WHO IS LIAM MOORE?
At 24-years-old, Moore is an experienced Championship centre-back who made his first breakthrough at Leicester City. He captained the Foxes' at youth level before joining the first team squad, debuting for them in January 2012.
After loan spells with Bradford City and Brentford in the English lower leagues, he established himself as a regular in Leicester's starting XI in 2013/14, courting interest from some of the country's top clubs along the way.
Moore remained on the club's books as they won the Premier League in 2015/16, though by that time he was more of a squad player and was once again out on loan, this time with Bristol City. Then, in the summer of 2016, he joined Reading on a permanent basis.
He was a key component in Jaap Stam's side, helping them reach the Championship playoff final where they lost on penalties to Huddersfield Town. He spoke openly of the impact his manager had on his personal progress last term, saying:
"Hopefully we can do the gaffer proud as every piece of information he's passed on to us this season has been vitally important and stuff we can take on board. Every week I feel like I've learnt something new from him and started to create good habits in my game. It's only good for me to be playing under him."
MOORE'S STRENGTHS AND WEAKNESSES
As centre-backs go, Moore is comfortable carrying the ball forward. He is fairly composed when under pressure and has no qualms driving on himself if given the space and time. In such instances he is able to call upon good pace and sound technique.
Perhaps learning from his Dutch manager, he is also intelligent in his movement and positioning when helping to build possession from the back.
Often he will move beyond his central defensive partner, Paul McShane, to offer a forward route to the Irishman and eliminate a pressing opponent.
Moore's willingness to drift and form a connection in possession is arguably more valuable to Reading's passing game than his actual ability on the ball. While capable, the range and accuracy of his passing is unspectacular.
Defensively, he is an aggressive marker who is willing to follow his opposite man up to the halfway line when appropriate. He does this with full knowledge that he has the athleticism to recover if necessary.
Despite a commanding stature – Moore stands at 6ft 1in – he is not dominant in the air; this season he has only won 54 per cent of his aerial duels. However, most of his main strengths are on the ground and with the ball at feet.
He is an excellent communicator who states his intentions when in possession and always looks to organise the team tactically.
This, along with his aforementioned movement and positioning, go a long way to explaining why only four Championship defenders have completed more passes than him this season.
WOULD MOORE FIT IN AT CELTIC?
Tactically, Moore would theoretically find it quite easy to settle at Celtic thanks to his current team's style of play.
averages more possession than the Royals' 55.6 per cent, while only three average more short passes per game than their 411.
In addition, Stam has shown a proclivity for switching from a back four to a back three, meaning Moore has experienced not only playing for a team that prioritises retention and use of the ball, but opt for different defensive shapes. In both respects, he is stylistically prepared for a move to Celtic.
Many of the Scottish titleholders' current centre-back options come with asterisks attached. Šimunović and Sviatchenko are injured; Mikael Lustig, Kieran Tierney and Nir Bitton prefer to play elsewhere; Kristoffer Ajer lacks experience. This meant he only natural, in form and fully fit central defender available to Brendan Rodgers at present is Dedryck Boyata.
This issue is only compounded by the fact that Celtic have successfully switched to a fluid 3-6-1 shape in recent weeks. Given performances and results in the new system, as well as their desire to go deep in the Europa League, they could do with another centre-back.
The good news is that Moore, as well as fitting their system and style, wouldn't break the bank. His contract with Reading lasts until 2021, so a free transfer isn't on the horizon, but reports suggest that the Championship club value him at £5million.
Paying that fee would make the Englishman the Scottish giants' biggest signing since they brought in Šimunović for over £6million in 2015/16. However, given they would be getting a finished article, not a prospect, it's a fee worth paying.
Moore has all the attributes to fit in at Celtic and, having played in the English Premier League and Championship, is of the level required to not only fill a temporary defensive void, but substantially improve their back line.
Who are the Favourites to Replace Neil Lennon if he Loses the Celtic Job?
Like father, like son: Ianis Hagi is ready for a return to the big time
Celtic goal machine Édouard can follow in Dembélé's footsteps
Time has proved Rodgers wasn't a monster for walking out on Celtic mid-season
How Rangers have put Gerrard on the path to succeeding Klopp at Liverpool
Why Premier League sides will be enticed by Scottish football's renaissance
Celtic's left-back search should end with Scotland international
Meling can ensure Celtic haven't been weakened by Tierney departure
Rangers full-back can make similar Premier League impact to Robertson
Sinclair legacy safe but time for Celtic to move on
Celtic can become home for well-travelled Elhamed
Analysing the three players on Celtic's right-back shortlist

redpajama_set_name: RedPajamaCommonCrawl


Have you been spending long hours in the gym taking grueling workouts only to be disappointed and frustrated by your lack of progress? Perhaps your lack of progress is due to low hormone production. Without question, hormones are the keys that unlock muscle growth and strength. Without an adequate and consistent supply of hormones, your muscle-building is dead in the water.
Here is just a partial list of the other great ingredients in GLAND-ALL : Vitamins & Minerals, Plant Sterols, Tongat Ali, Ginseng, Wild Yam, Bee Pollen, Smilax, Muira Puama, Enzymes, PAK, Dibencozide, Oriental Herbs, Saw Palmetto, KIC, Amino Acids and much more.
Read what Chiroprator Keith Wein D.C. had to say about Gland-All.
A little about me: I am a chiropractor and I just turned 50 years old. I have never been a real "muscle dude". Never used steroids, but I do like having same muscle definition and keeping strong.
In the past (about 10 years ago) I used Hot Stuff for a few months and had some great results. I had dropped weight and was feeling really good. In the past 2-3 years, my life has had a lot of stresses that have drawn me away from my workouts and proper diet such That I am now overweight.
When I received the email advertisement about Gland-All, I looked over the formula as I am very picky about my supplements. I had used glandulars before, from another company (Standard Process) and had some good results. Upon inspection, I realized that Gland-All is also a very good formula as a daily multiple vitamin with some amino's thrown in for good measure.
The price is what blew me away, so I figured why not give it a try. With my schedule, I can only get to the gym on Friday's, Saturday and Sunday's. I make a point of hitting at least 2 of the 3. I started Gland-All on Monday December 13th taking one Gland-All packet daily with a meal.
I noticed a difference in my energy levels within 3 days and on my Friday workout, I did not feeling like stopping! The same thing happened Saturday and Sunday. I did not increase my weigh at all but I did more reps than expected and did not have the soreness I would have expected on Monday.
By the way, I took advantage of your offer for Gland-All and bought the buy 2 get 1 free deal. I recommend this product to any guy needing an "extra" energy, especially someone in my age group (50+).
I take Hot Stuff products because they work. The Gland-All product seems to work giving me energy. I have only been taking one packet and will try two packs daily to see any change.
The glandulars are giving me great energy! My recocery time is superb! I am enjoying the results thus far!


Users with the customer service manager role can create a social media log entry for a case.
Only a manager or administrator can create an entry on the Social Logs related list, if necessary. The entries on this list are typically populated by the social integration tool.
Navigate to the desired Case form.
From the Social Logs related list, click New.
Fill in the fields on the Social Log form, as appropriate.
Social Profile The social profile for the customer contact or consumer.
Agent The agent participating in the conversation.
External ID The user's social media name or handle.
Document The related case number.
Message The details of the conversation.


text:
music / Electronic
Tri Angle Artist WIFE on His Sensual Debut Album: "I'm not afraid to tell someone I'm vulnerable."
The Irish ex-metal head has made one of the year's most intimate records.
By Ruth Saxelby
The former black metal frontman reveals his gentler, yet more powerful, side
There is nothing predictable about WIFE. Born James Kelly, he's the former frontman of black metal band Altar of Plagues, and has a degree in environmental science. He's the Tri Angle Records-signed artist who's bypassed the blurry beats trend to make a singer-songwriter album. And he's the tall, blokey guy with a twinkle in his eye who explores male vulnerability on his startlingly intimate debut album, What's Between. Its air is thick with a sexual tension that broods and questions, a mood born of rolling swathes of synth tones peppered with creeping industrial textures over which Kelly's voice flies in earnest as if on some spiritual quest. Kelly worked with labelmates Haxan Cloak and Lie on the production (as well as an earlier spell with ex-Vex'd producer Roly Porter), and their hyper-specific sonic aesthetic serves his almost folk music-like lyrics well. What's Between feels epic and awed, and gentle and powerful, all at once.
Kelly grew up in a working class family in the secluded Irish village of Ballinhassig, about 15 miles outside of Cork. "My parents didn't grow up in houses where you made art," he explains over a pint in a Brooklyn bar on a rainy day in May. "It wasn't a privilege they had. But I was very lucky that they always—even though they are not artistic themselves—nurtured that in me, told me to go wild with it, you know?" He moved to London three years ago, ostensibly to continue his studies ("I did my masters [degree] in conservation, which is a fancy word for save the whale," he says), but instead, it became the breeding ground for a new musical identity. After making three albums with Altar of Plagues that challenged the conventions of black metal, Kelly's growing creative frustration finally prompted him to go solo. His first release as WIFE was an EP called Stoic; the video to "Bodies" featured a half-naked Kelly tearing apart a peach with his hands and daubing ink up his arms in what seemed to be a deeply sensual, ritualistic act. For What's Between, he set out to make something closer to pop and the Irish music he'd grown up on. Kelly took singing lessons in the lead-up to the album's recording sessions, and while he says he wanted to sound "as good as I possibly could," what it ultimately gave him was the confidence to own the voice he has: "It's okay if I'm not the smooth R&B voice that everyone wants to hear—I'm just going to sing these songs that I have in me." Here, he talks about moving away from metal, exploring male vulnerability and being Irish.
How has your experience of Irish art and music shaped the album? The thing that's really appealing to me about Irish art, poetry and music is that it's quite raw—especially more traditional Irish music. One of my favorite Irish songs is Luke Kelly's "Raglan Road." It's him singing a poem, and it's this really raw, singer-songwriting type of thing. It's really emotive and powerful and poignant. Being Irish, I can often relate to the sentiment they're putting across in their music and the intent. That's where that comes from for me. I'm a very proud Irishman and I love Irish art. I love to explore it and be as inspired by it as I can.
Are there certain themes that run throughout Irish music? I'd say there's a duality to the Irish. We're either morose or we're partying. That's essentially what traditional Irish music is: it's either about the party or about the funeral. [Ireland] is not a hard place to live anymore—it is still hard because of the recession and things, but it's not like way back when it was an extremely poor country in the 1800s, or right through the 1900s, when there was all the political war going on. So we're kind of like the underdog, and that's kind of been ingrained in us and that comes across in our acts sometimes. But we're also proud, and I think pride is something that always comes across. With Irish music, when it's sad, it's sad in a really assured way. [On "Raglan Road," Kelly's] not sad like he's been beaten by his sadness; he's in control of it.
Was it a conscious decision that Irish music was something you were going to draw on? I think it was a case of looking at my cards and saying, "What do I have?" On one hand, I don't like to be overly conscious when I make music; I just want to make what's in me and get it out. But on the other hand, when you're doing something in the realm of pop music, you've got to be a bit more conscious that you're not sounding like someone else. Because Irish tradition is so close to my heart, it's natural for me to draw on it. This record, to me, is just a brutally honest expression of how I feel about certain things. Irish art does that so well.
"Rarely anymore are men presented as sensual. Like, as delicate and sensual."
You've moved from metal to experimental electronic music to something approaching pop. What's guiding that evolution? I think it's just one of those things. I've always been a songwriter, and it just so happened that for a couple years my songwriting was honed in on writing for a metal band, which was in many ways unplanned. When I lived at home in my parent's house, I was in my room making music all of the time, and it happened that the metal one was the one that stuck. [There was a] record deal and tours, and it's been year after year working on that. It came time to draw a line in the sand and take stock of what I've done so far; I really, really need to get this other stuff out of me. I couldn't see any way in which it would make sense for me to inject all the stuff that was inspiring me into a metal band. It just came to that point where I was just like, "I don't want to be in a metal band anymore; I need to pursue something else."
Do you see threads between your two incarnations, as Altar of Plagues and now as WIFE? Tonally I think they're both definitely residing in the moody side of things, for want of a better word. That's kind of what links them. I think what Altar of Plagues does that WIFE won't really touch on is really extreme aggression and anger and that sort of thing. What WIFE does that Altar of Plagues never did is that it can be happy. So, I've got the capacity for happiness.
The lyric about the world being darker in the light on album track "Dan Ce" is pretty epic. I think one of the premises of the whole record is the idea of lying and misrepresentation. It's not about a specific experience that I had; it's not about any one thing. But I sometimes think that we'd rather accept things that aren't true than know about what's really true, whether that's to do with a relationship with a person or related to something bigger, if you want to get into something political. We almost hide away from what's real and true, and stick with a façade. That's what that lyric relates to for me.
One thing that is key to your music is your presentation of male sexuality: it's intimate, sensual, and non-objectified. What prompted that? Rarely anymore are men presented as sensual. Like, as delicate and sensual. I don't think men are presented as being vulnerable—but men are extremely vulnerable and I think a lot of them are afraid to show that. The few that do are critiqued or mocked for it. In my mind the whole thing is a level playing field—if Miley Cyrus chooses to present herself a certain way, then she can, and I'm just gonna say that's how she wants to present herself. It's not her wanting to be sexualized. When I presented myself that way [in the "Bodies" video], it's me showing a visual representation of myself that is vulnerable.
It's also powerful—that power through vulnerability thing. Yeah, you know, I'm a big guy, but like I said, I'm not afraid to tell someone I'm vulnerable as fuck like anybody else. I don't need to be photographed being the meanest looking fella and then my interviews are me telling you how tough I am or whatever. I don't care about this stuff. I think sometimes men shy away from showing that side. I don't think there's anything wrong with it. It's a good, healthy thing to do.
What is sensuality to you? Just closeness, with anybody. It's the idea of taking away that veil we all hide behind and being really upfront in an emotional sense. Sensuality to me is more emotional than it is physical.
Wife RUTH SAXELBY
Electronic, RUTH SAXELBY, Tri Angle Records, Wife
music / Reggae
How Blink-182's Travis Barker became rap's favorite drummer


This button lock folder from Scott Sawby features a mirror polished spear point blade with false top edge and dual checkered thumbstuds. The handle is comprised of mirror polished dovetailed stainless steel bolsters and pommel with desert ironwood scales over fileworked stainless steel liners and a stainless steel backspacer. Minor scuffs on blade and bolsters, but overall excellent condition. Includes padded and zippered case.


Gurgaon has recently come to be the business hub of New Delhi – with global companies, business complexes and shopping malls covering the cityscape. But though being a business oriented area, Gurgaon also has several places of tourist interest like the Sultanpur Bird Sanctuary, Damdama Lake and Shama nearby. Gurgaon is well linked by rail and road to Delhi, Faridabad and Jaipur.
Follow airport exit signage for Delhi Cantt. After first U-turn follow signage for Gurgaon. Take a right turn at first major signal under the Expressway to join National Highway 8 going to Gurgaon. Follow the expressway signage for Gurgaon over two over bridges up to the toll plaza. Bear Left immediately after crossing the Toll Plaza to take Exit 5. Follow the slip road and take the second U-turn towards Shankar Chowk. Turn left at the crossing and go straight for 50 metres. The hotel entrance is the first gate on the left.
From the International Airport main exit follow initial signage for city for 1 km up to first traffic signal. After the signal take right hand fork sign posted for Gurgaon up to the roundabout. At roundabout turn right under the flyover to take the entry lane to the expressway. Follow the expressway signage for Gurgaon over one bridge up to the toll plaza. Bear Left immediately after crossing the Toll Plaza to take Exit 5. Follow the slip road and take the second U-turn towards Shankar Chowk. Turn left at the crossing and go straight for 50 metres. The hotel entrance is the first gate on the left.


I answered questions chosen at random by Greg Perkins impromptu on 15 June 2014. You can listen to or download the podcast of just this section below – or check out the whole episode of Philosophy in Action Radio.
What is the opposite of egalitarianism? Elitism? Differentialism? Hierarchism? Justice?
Is it ever just to 'make an example' of a criminal?
Would you ever consider doing a TED lecture? If so, what would it be about?


The Hermitage School District is pleased to make the PowerSchool Parent Portal available to our parents. You should have received a letter containing an account code for each of your students, as well as your student's login credentials. Please keep this code in a safe place as it does not expire and can be used to create additional accounts. Additionally, it is strongly recommended that you login to your student's account and change their password even if they are young or may not use the account. If you do not change their password, their portal account and their records could be accessed. Once logged in, go to the 'Account Preferences' option to change the password.


text:
Q: React Native Invalid Product ID in In-App Purchases this is my code where i am getting products added on app store. before i was was working fine. when i remove the previous products on app store and added new then it's stop working. i removed the previous products from app store but still i can get that products by using their id. i clear build restart xcode but nothing works.
  const itemSkus = Platform.select({
    ios: ['pkg01', 'pkg02'],
    android: ['pkg01', 'pkg02'],
  });
  useEffect(() => {
    initializeConnection();

    purchaseUpdateSubscription = purchaseUpdatedListener(async purchase => {
      const receipt = purchase.transactionReceipt;
      if (receipt) {
        try {
          if (Platform.OS === 'ios') {
            RNIap.finishTransactionIOS(purchase.transactionId);
          }
          console.log('receipt: ', purchase.transactionReceipt);
        } catch (e) {
          console.warn(e);
        }
      }
    });
  }, []);

  const initializeConnection = async () => {
    try {
      const result = await RNIap.initConnection();
      console.log('connection is => ', result);

      if (result) {
        await getProducts()
      }
    } catch (err) {
      console.log('error in cdm => ', err);
    }
  };
  const getProducts = async () => {
     const products = await RNIap.getProducts(itemSkus);
      console.log('Products', products);
      setProductList(products);
  }

A: This might be a combination of a few things:

*

*Apple could be caching the old product IDs, it may take some time but they will become unavailable.

*The new product IDs might need to be reviewed/approved by Apple to ensure they abide by their rules before they are made available. Until that happens you won't be able to access them for in app purchases.

redpajama_set_name: RedPajamaStackExchange


Fancy Black Vanity Table IKEA and Remarkable Black Vanity Table With Black Vanity Table Ikea Theltco is among images of Furniture ideas for your house. The resolution of Fancy Black Vanity Table IKEA and Remarkable Black Vanity Table With Black Vanity Table Ikea Theltco is 800×600 pixels. Along with suggestions concerning Furniture and Home Design Ideas. You could discover the other picture or post pertaining to Black Vanity Table IKEA simply push the gallery or if you are interested in comparable images of Fancy Black Vanity Table IKEA and Remarkable Black Vanity Table With Black Vanity Table Ikea Theltco, you are cost-free to browse through search feature that situated on the top this page. If you are pleased, please share this link to social networks to earn the people near you are additionally influenced. We wish a few of the style below could include in the appeal of your house.
Enchanting Black Vanity Table IKEA and Vanity Table Ikea To Elegant Black Vanity Table Makeup Vanity Table. Lovely Black Vanity Table IKEA and Linnmon Alex Table Black Brown Gray Wish Lists Home Decoration. Enchanting Black Vanity Table IKEA and Ikea Black Vanity Champagne Dual Cabinets Vanity Table Set Ikea. Elegant Black Vanity Table IKEA and Brimnes Dressing Table Ikea. Catchy Black Vanity Table IKEA and Black Vanity Table Ikea Image Home Design Ideas. Collection in Black Vanity Table IKEA and Malm Dressing Table Black Brown Ikea.
If you want to use this image click the download image link below to go to the download page. Right click the image and select "Save Image As" to download the Fancy Black Vanity Table IKEA and Remarkable Black Vanity Table With Black Vanity Table Ikea Theltco to your computer or select "Set Desktop Background As" if your browser has that capability.
Thanks visiting our site, If you located any kind of images copyrighted to your own, please call us, and we will certainly remove it. We do not intend to show any kind of copyright secured images. We hope you could discover exactly what you need right here. We always effort to show a picture with HD resolution or a minimum of with perfect pictures. The Fancy Black Vanity Table IKEA and Remarkable Black Vanity Table With Black Vanity Table Ikea Theltco can be the beneficial inspiration for those that look for an image inning accordance with distinct groups. Lastly, all images we have been displayed on this site will certainly influence you all.


The Boeing C-22 military transport is a modification of Boeing's 727-100 commercial airliner. The picture below depicts a Boeing C-22B, three of these were built and used by the 201st Airlift Squadron, District of Columbia Air National Guard as it's primary medium-range personnel transport.
This picture of a Boeing C-22 has been digitally re-mastered from a USAF picture and they should be credited wherever it is used. We only authorise non-commercial use of the information on this page and we particularly encourage it's use for educational purposes.