What triggers transcription in DNA?
Primary transcript
The steps contributing to the production of primary transcripts involve a series of molecular interactions that initiate transcription of DNA within a cell's nucleus. Based on the needs of a given cell, certain DNA sequences are transcribed to produce a variety of RNA products to be translated into functional proteins for cellular use. To initiate the transcription process in a cell's nucleus, DNA double helices are unwound and hydrogen bonds connecting compatible nucleic acids of DNA are broken to produce two unconnected single DNA strands. One strand of the DNA template is used for transcription of the single-stranded primary transcript mRNA. This DNA strand is bound by an RNA polymerase at the promoter region of the DNA.
Cell nucleus
Since the nucleus is the site of transcription, it also contains a variety of proteins that either directly mediate transcription or are involved in regulating the process. These proteins include helicases, which unwind the double-stranded DNA molecule to facilitate access to it, RNA polymerases, which bind to the DNA promoter to synthesize the growing RNA molecule, topoisomerases, which change the amount of supercoiling in DNA, helping it wind and unwind, as well as a large variety of transcription factors that regulate expression.
Transcription bubble
The addition and pairing of nitrogenous bases are the two main processes that take place in the transcription bubble, and both of these processes are controlled by the RNA Polymerase enzyme. These processes take place in the elongation phase of the RNA strand. As RNA polymerase progresses down the DNA template strand in the 3' to 5' direction (the DNA coding strand in the 5' to 3' direction), more of the double stranded DNA is unwound downstream of the polymerase (towards the 5' end of the template strand or 3' end of the coding strand) while DNA upstream of the polymerase (towards the 3' end of the template strand or 5' end of the coding strand) re-anneals. Since DNA has a helical structure, the movement of transcription bubble during RNA synthesis requires the DNA strand to be consistently rotated. This process is also controlled by RNA Polymerase.
Promoter (genetics)
The initiation of the transcription is a multistep sequential process that involves several mechanisms: promoter location, initial reversible binding of RNA polymerase, conformational changes in RNA polymerase, conformational changes in DNA, binding of nucleoside triphosphate (NTP) to the functional RNA polymerase-promoter complex, and nonproductive and productive initiation of RNA synthesis.
Transcriptional regulation
The transcription of a basic prokaryotic gene is dependent on the strength of its promoter and the presence of activators or repressors. In the absence of other regulatory elements, a promoter’s sequence-based affinity for RNA polymerases varies, which results in the production of different amounts of transcript. The variable affinity of RNA polymerase for different promoter sequences is related to regions of consensus sequence upstream of the transcription start site. The more nucleotides of a promoter that agree with the consensus sequence, the stronger the affinity of the promoter for RNA Polymerase likely is.
Eukaryotic transcription
When transcription is arrested by the presence of a lesion in the transcribed strand of a gene, DNA repair proteins are recruited to the stalled RNA polymerase to initiate a process called transcription-coupled repair. Central to this process is the general transcription factor TFIIH that has ATPase activity. TFIIH causes a conformational change in the polymerase, to expose the transcription bubble trapped inside, in order for the DNA repair enzymes to gain access to the lesion. Thus, RNA polymerase serves as damage-sensing protein in the cell to target repair enzymes to genes that are being actively transcribed.
Activating transcription factor 2
This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun and stimulates CRE-dependent transcription. The protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. Additional transcript variants have been identified but their biological validity has not been determined.
Primary transcript
Research has also led to greater knowledge about certain diseases related to changes within primary transcripts. One study involved estrogen receptors and differential splicing. The article entitled, "Alternative splicing of the human estrogen receptor alpha primary transcript: mechanisms of exon skipping" by Paola Ferro, Alessandra Forlani, Marco Muselli and Ulrich Pfeffer from the laboratory of Molecular Oncology at National Cancer Research Institute in Genoa, Italy, explains that 1785 nucleotides of the region in the DNA that codes for the estrogen receptor alpha (ER-alpha) are spread over a region that holds more than 300,000 nucleotides in the primary transcript. Splicing of this pre-mRNA frequently leads to variants or different kinds of the mRNA lacking one or more exons or regions necessary for coding proteins. These variants have been associated with breast cancer progression. In the life cycle of retroviruses, proviral DNA is incorporated in transcription of the DNA of the cell being infected. Since retroviruses need to change their pre-mRNA into DNA so that this DNA can be integrated within the DNA of the host it is affecting, the formation of that DNA template is a vital step for retrovirus replication. Cell type, the differentiation or changed state of the cell, and the physiological state of the cell, result in a significant change in the availability and activity of certain factors necessary for transcription. These variables create a wide range of viral gene expression. For example, tissue culture cells actively producing infectious virions of avian or murine leukemia viruses (ASLV or MLV) contain such high levels of viral RNA that 5–10% of the mRNA in a cell can be of viral origin. This shows that the primary transcripts produced by these retroviruses do not always follow the normal path to protein production and convert back into DNA in order to multiply and expand.
Transcription factor II B
After DNA melting the Inr must be located on the DNA so the TSS can be identified by the RNA polymerase II and transcription can begin. This is done by passing the DNA through the 'template tunnel' and the DNA is scanned, looking for the Inr and placing it in a position that ensures the transcription start site is located in the correct place by the RNA polymerase active site. The B reader of TFIIB is found in the template tunnel and is important in locating the Inr, mutations in the B reader cause the TSS to change and therefore incorrect transcription to occur (although PIC formation and DNA melting still take place). Yeast are a particularly good example of this alignment as the yeast Inr motif has a strictly conserved A residue at position 28 and in the open complex model a complimentary T residue can be found in the B reader helix. When this T residue is mutated, transcription was significantly less effective emphasizing the role of the B reader.
ADP-ribosylation
The organization of nucleosomes is key to regulation of gene expression: the spacing and organization of nucleosomes changes what regions of DNA are available for transcription machinery to bind and transcribe DNA. PARP1, a poly-ADP ribose polymerase, has been shown to affect chromatin structure and promote changes in the organization of nucleosomes through modification of histones. 
PARPs have been shown to affect transcription factor structure and cause recruitment of many transcription factors to form complexes at DNA and elicit transcription.Mono ADP-ribosyltransferases are also shown to affect transcription factor binding at promoters. For example, PARP14, a mono ADP-ribosyltransferase, has been shown to affect STAT transcription factor binding.
HIV
Two RNA genomes are encapsidated in each HIV-1 particle (see Structure and genome of HIV). Upon infection and replication catalyzed by reverse transcriptase, recombination between the two genomes can occur. Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle the genetic information that is transmitted from parental to progeny genomes.
Transcription factor
Transcription factors can also be used to alter gene expression in a host cell to promote pathogenesis. A well studied example of this are the transcription-activator like effectors (TAL effectors) secreted by Xanthomonas bacteria. When injected into plants, these proteins can enter the nucleus of the plant cell, bind plant promoter sequences, and activate transcription of plant genes that aid in bacterial infection. TAL effectors contain a central repeat region in which there is a simple relationship between the identity of two critical residues in sequential repeats and sequential DNA bases in the TAL effector’s target site. This property likely makes it easier for these proteins to evolve in order to better compete with the defense mechanisms of the host cell.
Transcription (biology)
The stretch of DNA transcribed into an RNA molecule is called a "transcription unit" and encodes at least one gene. If the gene encodes a protein, the transcription produces messenger RNA (mRNA); the mRNA, in turn, serves as a template for the protein's synthesis through translation. Alternatively, the transcribed gene may encode for non-coding RNA such as microRNA, ribosomal RNA (rRNA), transfer RNA (tRNA), or enzymatic RNA molecules called ribozymes. Overall, RNA helps synthesize, regulate, and process proteins; it therefore plays a fundamental role in performing functions within a cell.
Frameshift mutation
After DNA replication, the reading of a selected section of genetic information is accomplished by transcription.
Nucleotides containing the genetic information are now on a single strand messenger template called mRNA. The mRNA is incorporated with a subunit of the ribosome and interacts with an rRNA. The genetic information carried in the codons of the mRNA are now read (decoded) by anticodons of the tRNA. As each codon (triplet) is read, amino acids are being joined together until a stop codon (UAG, UGA or UAA) is reached. At this point the polypeptide (protein) has been synthesised and is released. For every 1000 amino acid incorporated into the protein, no more than one is incorrect. This fidelity of codon recognition, maintaining the importance of the proper reading frame, is accomplished by proper base pairing at the ribosome A site, GTP hydrolysis activity of EF-Tu a form of kinetic stability, and a proofreading mechanism as EF-Tu is released.
TADA2L
Many DNA-binding transcriptional activator proteins enhance the initiation rate of RNA polymerase II-mediated gene transcription by interacting functionally with the general transcription machinery bound at the basal promoter. Adaptor proteins are usually required for this activation, possibly to acetylate and destabilize nucleosomes, thereby relieving chromatin constraints at the promoter. The protein encoded by this gene is a transcriptional activator adaptor and has been found to be part of the PCAF histone acetylase complex. Two transcript variants encoding different isoforms have been identified for this gene.
DNA-binding protein
DNA-binding proteins include transcription factors which modulate the process of transcription, various polymerases, nucleases which cleave DNA molecules, and histones which are involved in chromosome packaging and transcription in the cell nucleus. DNA-binding proteins can incorporate such domains as the zinc finger, the helix-turn-helix, and the leucine zipper (among many others) that facilitate binding to nucleic acid. There are also more unusual examples such as transcription activator like effectors.
Primary transcript
A number of factors contribute to the activation and inhibition of transcription and therefore regulate the production of primary transcripts from a given DNA template.
HIV
Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the positive-sense single-stranded RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA) molecule. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow the virus to evade the body's immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a sense DNA from the "antisense" cDNA. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus. The integration of the viral DNA into the host cell's genome is carried out by another viral enzyme called integrase.
Transcription bubble
A transcription bubble is a molecular structure that is formed during the transcription of DNA when a limited portion of the DNA double strand is unwound. The Transcription bubble ranges from around 12-14 base pairs, but can be upto 17 base pairs. The transcription bubble is formed by the RNA Polymerase when the enzyme binds with a promoter. The σ factor, or sigma factor, is subunit that assists in the process of transcription, and this subunit stabilizes the transcription bubble when it binds to the unpaired bases. The RNA Polymerase binds to the exposed DNA and begins to synthesize the new strand of RNA.
DNA polymerase V
Transcription of the SOS response genes is negatively regulated by the LexA repressor. LexA binds to the promoter of the UmuDC operon and inhibits gene transcription. DNA damage in the cell leads to the formation of RecA*. RecA* interacts with LexA and stimulates its proteolytic activity, which leads to the autocleavage of the repressor freeing the operon for transcription. The UmuDC operon is transcribed and translated into UmuC and UmuD.
TAF1
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor TFIID, which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme. Two transcripts encoding different isoforms have been identified for this gene.
Histones are often acetylated to open DNA for transcription. TAF1 contains two bromodomains, which each can bind one of two acetyllysine residues at position 5 and 12 in the H4 tail, to stabilize the TBP-TATA box complex.
Coactivator (genetics)
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA promoter site or a specific DNA regulatory sequence called an enhancer. Binding of the activator-coactivator complex increases the speed of transcription by recruiting general transcription machinery to the promoter, therefore increasing gene expression. The use of activators and coactivators allows for highly specific expression of certain genes depending on cell type and developmental stage.
Epigenetics
One mode of thinking is that this tendency of acetylation to be associated with "active" transcription is biophysical in nature. Because it normally has a positively charged nitrogen at its end, lysine can bind the negatively charged phosphates of the DNA backbone. The acetylation event converts the positively charged amine group on the side chain into a neutral amide linkage. This removes the positive charge, thus loosening the DNA from the histone. When this occurs, complexes like SWI/SNF and other transcriptional factors can bind to the DNA and allow transcription to occur. This is the "cis" model of epigenetic function. In other words, changes to the histone tails have a direct effect on the DNA itself.
Recombination hotspot
Homologous recombination in functional regions of DNA is strongly stimulated by transcription, as observed in a range of different organisms. Transcription associated recombination appears to be due, at least in part, to the ability of transcription to open the DNA structure and enhance accessibility of DNA to exogenous chemicals and internal metabolites that cause recombinogenic DNA damages. These findings suggest that transcription-associated recombination may contribute significantly to recombination hotspot formation.
Chromatin remodeling
The transcriptional regulation of the genome is controlled primarily at the preinitiation stage by binding of the core transcriptional machinery proteins (namely, RNA polymerase, transcription factors, and activators and repressors) to the core promoter sequence on the coding region of the DNA. However, DNA is tightly packaged in the nucleus with the help of packaging proteins, chiefly histone proteins to form repeating units of nucleosomes which further bundle together to form condensed chromatin structure. Such condensed structure occludes many DNA regulatory regions, not allowing them to interact with transcriptional machinery proteins and regulate gene expression. To overcome this issue and allow dynamic access to condensed DNA, a process known as chromatin remodeling alters nucleosome architecture to expose or hide regions of DNA for transcriptional regulation.
Activator (genetics)
A transcriptional activator is a protein (transcription factor) that increases gene transcription of a gene or set of genes. Most activators are DNA-binding proteins that bind to enhancers or promoter-proximal elements.
Transcription factor II H
(NER)TFIIH is a general transcription factor that acts to recruit RNA Pol II to the promoters of genes.  It functions as a helicase that unwinds DNA.  It also unwinds DNA after a DNA lesion has been recognized by either the global genome repair (GGR) pathway or the transcription-coupled repair (TCR) pathway of NER. Also, the purified TFIIH has role in making RNA by activating enzyme a-amanitin.
DNA
Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.
Active chromatin sequence
An active chromatin sequence (ACS) is a region of DNA in a eukaryotic chromosome in which histone modifications such as acetylation lead to exposure of the DNA sequence thus allowing binding of transcription factors and transcription to take place. Active chromatin may also be called euchromatin. ACSs may occur in non-expressed gene regions which are assumed to be "poised" for transcription. The sequence once exposed often contains a promoter to began transcription. At this site acetylation or methylation can take place causing a conformational change to the chromatin. At the active chromatin sequence site deacetylation can caused the gene to be repressed if not being expressed.
Eukaryotic transcription
The two main tasks of transcription initiation are to provide RNA polymerase with an access to the promoter and to assemble general transcription factors with polymerase into a transcription initiation complex. Diverse mechanisms of initiating transcription by overriding inhibitory signals at the gene promoter have been identified. Eukaryotic genes have acquired extensive regulatory sequences that encompass a large number of regulator-binding sites and spread overall kilobases (sometimes hundreds of kilobases) from the promoter–-both upstream and downstream. The regulator binding sites are often clustered together into units called enhancers. Enhancers can facilitate highly cooperative action of several transcription factors (which constitute enhanceosomes). Remote enhancers allow transcription regulation at a distance. Insulators situated between enhancers and promoters help define the genes that an enhancer can or cannot influence.
Gene expression
The production of the RNA copy of the DNA is called transcription, and is performed in the nucleus by RNA polymerase, which adds one RNA nucleotide at a time to a growing RNA strand as per the complementarity law of the bases. This RNA is complementary to the template 3' → 5' DNA strand, which is itself complementary to the coding 5' → 3' DNA strand. Therefore, the resulting 5' → 3' RNA strand is identical to the coding DNA strand with the exception that Thymines are replaced with uracils (U) in the RNA. A coding DNA strand reading "ATG" is indirectly transcribed through the non-coding strand as "UAC" in RNA.
Phase variation
Transcriptional regulation (bottom portion of figure) occurs in several ways. One possible way is if the repeats are located in the promoter region at the RNA polymerase binding site, -10 and -35 upstream of the gene(s). The opportunistic pathogen "H. influenzae" has two divergently oriented promoters and fimbriae genes "hifA" and "hifB". The overlapping promoter regions have repeats of the dinucleotide TA in the -10 and -35 sequences. Through SSM the TA repeat region can undergo addition or subtraction of TA dinucleotides which results in the reversible ON phase or OFF phase of transcription of the "hifA" and "hifB". The second way that SSM induces transcriptional regulation is by changing the short repeat sequences located outside the promoter. If there is a change in the short repeat sequence it can affect the binding of a regulatory protein, such as an activator or repressor. It can also lead to differences in post-transcriptional stability of mRNA.
Eukaryotic transcription
Transcription elongation is not a smooth ride along the DNA railway. For proofreading, the polymerase is made to back-up, erase some of the RNA it has already made and have another go at transcription. In general, RNA polymerase does not transcribe through a gene at a constant pace. Rather it pauses periodically at certain sequences, sometimes for long periods of time before resuming transcription. In extreme cases, for example, when the polymerase encounters a damaged nucleotide, it comes to a complete halt. More often, an elongating polymerase is stalled near the promoter. Promoter-proximal pausing during early elongation is a commonly used mechanism for regulating genes poised to be expressed rapidly or in a coordinated fashion. Pausing is mediated by a complex called NELF (negative elongation factor) in collaboration with DSIF (DRB-sensitivity-inducing factor containing SPT4/SPT5). The blockage is released once the polymerase receives an activation signal, such as the phosphorylation of Ser-2 of CTD tail by P-TEFb. Other elongation factors such as ELL and TFIIS stimulate the rate of elongation by limiting the length of time that polymerase pauses.
Transcription coregulator
In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription. In humans several dozen to several hundred coregulators are known, depending on the level of confidence with which the characterisation of a protein as a coregulator can be made. One class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP dependent class modifies the conformation of chromatin.
Initiator element
The initiator element (Inr) is the most common sequence found at the transcription start site of eukaryotic genes. It is a 17 bp element. Inr in humans was first explained and sequenced by two MIT biologists, Stephen T. Smale and David Baltimore in 1989. Their research showed that Inr promotor is able to initiate basal transcription in absence of the TATA box. In the presence of a TATA box or other promoters, the Inr increases the efficiency of transcription by working alongside the promoters to bind RNA polymerase II. A gene with both types of promoters will have higher promoter binding strength, easier activation and higher levels of transcription activity. The TFIID, which is a component of the RNA polymerase II preinitiation complex binds to both the TATA box and Inr. Two subunits, TAF1 and TAF2, of the TFIID recognize the Inr sequence and bring the complex together. The interaction between TFIID and Inr is believed to be most imperative in initiating transcription. This is likey due to the Inr sequence overlapping the start site. The Inr element is also believed to interact with activator Sp1, specificity protein 1 transcription factor. Sp1 is then able to regulate the activation and initiation of transcription
Eukaryotic transcription
After escaping the promoter and shedding most of the transcription factors for initiation, the polymerase acquires new factors for the next phase of transcription: elongation. Transcription elongation is a processive process. Double stranded DNA that enters from the front of the enzyme is unzipped to avail the template strand for RNA synthesis. For every DNA base pair separated by the advancing polymerase, one hybrid RNA:DNA base pair is immediately formed. DNA strands and nascent RNA chain exit from separate channels; the two DNA strands reunite at the trailing end of the transcription bubble while the single strand RNA emerges alone.
Transactivation
Artificial transactivation of a gene is achieved by inserting it into the genome at the appropriate area as transactivator gene adjoined to special promoter regions of DNA. The transactivator gene expresses a transcription factor that binds to specific promoter region of DNA. By binding to the promoter region of a gene, the transcription factor causes that gene to be expressed. The expression of one transactivator gene can activate multiple genes, as long as they have the same, specific promoter region attached. Because the expression of the transactivator gene can be controlled, transactivation can be used to turn genes on and off. If this specific promoter region is also attached to a reporter gene, we can measure when the transactivator is being expressed.
RNA polymerase II
Oxidative DNA damage may block RNA polymerase II transcription and cause strand breaks. An RNA templated transcription-associated recombination process has been described that can protect against DNA damage. During the G1/G0 stages of the cell cycle, cells exhibit assembly of homologous recombination factors at double-strand breaks within actively transcribed regions. It appears that transcription is coupled to repair of DNA double-strand breaks by RNA templated homologous recombination. This repair process efficiently and accurately rejoins double-strand breaks in genes being actively transcribed by RNA polymerase II.
Long non-coding RNA
NcRNAs also target general transcription factors required for the RNAP II transcription of all genes. These general factors include components of the initiation complex that assemble on promoters or involved in transcription elongation. A ncRNA transcribed from an upstream minor promoter of the dihydrofolate reductase (DHFR) gene forms a stable RNA-DNA triplex within the major promoter of DHFR to prevent the binding of the transcriptional co-factor TFIIB. This novel mechanism of regulating gene expression may in fact represent a widespread method of controlling promoter usage given that thousands of such triplexes exist in eukaryotic chromosome. The U1 ncRNA can induce transcription initiation by specifically binding to and stimulating TFIIH to phosphorylate the C-terminal domain of RNAP II. In contrast the ncRNA 7SK, is able to repress transcription elongation by, in combination with HEXIM1/2, forming an inactive complex that prevents the PTEFb general transcription factor from phosphorylating the C-terminal domain of RNAP II, thereby repressing global elongation under stressful conditions. These examples, which bypass specific modes of regulation at individual promoters to mediate changes directly at the level of initiation and elongation transcriptional machinery, provide a means of quickly affecting global changes in gene expression.
Introduction to genetics
The information in DNA is held in the sequence of the repeating units along the DNA chain. These units are four types of nucleotides (A,T,G and C) and the sequence of nucleotides stores information in an alphabet called the genetic code. When a gene is read by a cell the DNA sequence is copied into a very similar molecule called RNA (this process is called transcription). Transcription is controlled by other DNA sequences (such as promoters), which show a cell where genes are, and control how often they are copied. The RNA copy made from a gene is then fed through a structure called a ribosome, which translates the sequence of nucleotides in the RNA into the correct sequence of amino acids and joins these amino acids together to make a complete protein chain. The new protein then folds up into its active form. The process of moving information from the language of RNA into the language of amino acids is called translation.
DNA footprinting
The regulation of transcription has been studied extensively, and yet there is still much that is not known. Transcription factors and associated proteins that bind promoters, enhancers, or silencers to drive or repress transcription are fundamental to understanding the unique regulation of individual genes within the genome. Techniques like DNA footprinting help elucidate which proteins bind to these associated regions of DNA and unravel the complexities of transcriptional control.
Biochemical cascade
The cellular response in signal transduction cascades involves alteration of the expression of effector genes or activation/inhibition of targeted proteins. Regulation of protein activity mainly involves phosphorylation/dephosphorylation events, leading to its activation or inhibition. It is the case for the vast majority of responses as a consequence of the binding of the primary messengers to membrane receptors. This response is quick, as it involves regulation of molecules that are already present in the cell. On the other hand, the induction or repression of the expression of genes requires the binding of transcriptional factors to the regulatory sequences of these genes. The transcriptional factors are activated by the primary messengers, in most cases, due to their function as nuclear receptors for these messengers. The secondary messengers like DAG or Ca could also induce or repress gene expression, via transcriptional factors. This response is slower than the first because it involves more steps, like transcription of genes and then the effect of newly formed proteins in a specific target. The target could be a protein or another gene.
Eukaryotic transcription
Eukaryotic transcription is the elaborate process that eukaryotic cells use to copy genetic information stored in DNA into units of RNA replica. Gene transcription occurs in both eukaryotic and prokaryotic cells. Unlike prokaryotic RNA polymerase that initiates the transcription of all different types of RNA, RNA polymerase in eukaryotes (including humans) comes in three variations, each encoding a different type of gene. A eukaryotic cell has a nucleus that separates the processes of transcription and translation. Eukaryotic transcription occurs within the nucleus where DNA is packaged into nucleosomes and higher order chromatin structures. The complexity of the eukaryotic genome necessitates a great variety and complexity of gene expression control.
CAAT box
The CAAT box is what is known as a core promoter, also known as the basal promoter or simply the promoter, is a region of DNA that initiates transcription of a particular gene. This region, in particular for the CAAT box, is located about 60–100 bases upstream (towards the 5' end), however no less than 27 base pairs away, from the initial transcription site or a eukaryote gene in which a complex of general transcription factors bind with RNA polymerase II prior to the initiation of transcription. It is essential to the transcription that these core binding factors (also referred to as nuclear factor Y or NF-Y) are able to bind to the CCAAT motif. Experiments in many laboratories have shown that mutations to the CCAAT motif that cause a loss of CBF binding also decreases transcriptional activity in these promoters, suggesting that CBF-CCAAT complexes are essential for optimum transcriptional activity.
DNA
In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (4 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.
MED1
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes [e.g., thyroid hormone receptor-(TR-) associated proteins that interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors]. It also regulates p53-dependent apoptosis and it is essential for adipogenesis. This protein is known to have the ability to self-oligomerize.
DACH1
Transcription. DACH1 conducts transcriptional function through interacting with transcription factors including c-Jun, estrogen receptor alpha, the androgen receptor, and the basal transcription apparatus through binding to the co-integrator protein CA150. Curiously, DACH1 selectively bound to the delta domain of c-Jun, which was known to interact with an endogenous cellular repressor. DACH1 binds directly with a Forkhead-like DNA sequence to restrain oncogenic signals from a subset of FKHR proteins. Dach1 governs mRNA translation of an EMT signature and governs Snail1 transcription.
General transcription factor
The transcription preinitiation complex is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. It attaches to the promoter of the DNA (e.i., TATA box) and helps position the RNA polymerase II to the gene transcription start sites, denatures the DNA, and then starts transcription.
Transcription factor
Transcription factors are one of the groups of proteins that read and interpret the genetic "blueprint" in the DNA. They bind to the DNA and help initiate a program of increased or decreased gene transcription. As such, they are vital for many important cellular processes. Below are some of the important functions and biological roles transcription factors are involved in:
Transcription elongation regulator 1
This gene encodes a nuclear protein that regulates transcriptional elongation and pre-mRNA splicing. The encoded protein interacts with the hyperphosphorylated C-terminal domain of RNA polymerase II via multiple FF domains, and with the pre-mRNA splicing factor SF1 via a WW domain. Alternative splicing results in multiple transcripts variants encoding different isoforms.
Eukaryotic transcription
The initiation of gene transcription in eukaryotes occurs in specific steps. First, an RNA polymerase along with general transcription factors binds to the promoter region of the gene to form a closed complex called the preinitiation complex. The subsequent transition of the complex from the closed state to the open state results in the melting or separation of the two DNA strands and the positioning of the template strand to the active site of the RNA polymerase. Without the need of a primer, RNA polymerase can initiate the synthesis of a new RNA chain using the template DNA strand to guide ribonucleotide selection and polymerization chemistry. However, many of the initiated syntheses are aborted before the transcripts reach a significant length (~10 nucleotides). During these abortive cycles, the polymerase keeps making and releasing short transcripts until it is able to produce a transcript that surpasses ten nucleotides in length. Once this threshold is attained, RNA polymerase passes the promoter and transcription proceeds to the elongation phase.
Terminator (genetics)
In eukaryotic transcription of mRNAs, terminator signals are recognized by protein factors that are associated with the RNA polymerase II and which trigger the termination process. Once the poly-A signals are transcribed into the mRNA, the proteins cleavage and polyadenylation specificity factor (CPSF) and cleavage stimulation factor (CstF) transfer from the carboxyl terminal domain of RNA polymerase II to the poly-A signal. These two factors then recruit other proteins to the site to cleave the transcript, freeing the mRNA from the transcription complex, and add a string of about 200 A-repeats to the 3' end of the mRNA in a process known as polyadenylation. During these processing steps, the RNA polymerase continues to transcribe for several hundred to a few thousand bases and eventually dissociates from the DNA and downstream transcript through an unclear mechanism; there are two basic models for this event known as the torpedo and allosteric models.
Transcription factor II A
Transcription factor TFIIA is a nuclear protein involved in the RNA polymerase II-dependent transcription of DNA. TFIIA is one of several general (basal) transcription factors (GTFs) that are required for all transcription events that use RNA polymerase II. Other GTFs include TFIID, a complex composed of the TATA binding protein TBP and TBP-associated factors (TAFs), as well as the factors TFIIB, TFIIE, TFIIF, and TFIIH. Together, these factors are responsible for promoter recognition and the formation of a transcription preinitiation complex (PIC) capable of initiating RNA synthesis from a DNA template.
DNA-binding protein
In contrast, other proteins have evolved to bind to specific DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one specific set of DNA sequences and activates or inhibits the transcription of genes that have these sequences near their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This alters the accessibility of the DNA template to the polymerase.
Eukaryotic transcription
General transcription factors are a group of proteins involved in transcription initiation and regulation. These factors typically have DNA-binding domains that bind specific sequence elements of the core promoter and help recruit RNA polymerase to the transcriptional start site.
General transcription factors for RNA polymerase II include TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH.
RNA polymerase II holoenzyme
Transcription begins with matching of NTPs to the first and second in the DNA sequence. This, like most of the remainder of transcription, is an energy-dependent process, consuming adenosine triphosphate (ATP) or other NTP.
TATA box
This cluster of RNA polymerase II and various transcription factors is known as the basal transcriptional complex (BTC). In this state, it only gives a low level of transcription. Other factors must stimulate the BTC to increase transcription levels. One such example of a BTC stimulating region of DNA is the CAAT box. Additional factors, including the Mediator complex, transcriptional regulatory proteins, and nucleosome-modifying enzymes also enhance transcription "in vivo".
Transcription (biology)
RNA polymerase, assisted by one or more general transcription factors, then selects a transcription start site in the transcription bubble, binds to an initiating NTP and an extending NTP (or a short RNA primer and an extending NTP) complementary to the transcription start site sequence, and catalyzes bond formation to yield an initial RNA product.
Transcription (biology)
Some viruses (such as HIV, the cause of AIDS), have the ability to transcribe RNA into DNA. HIV has an RNA genome that is "reverse transcribed" into DNA. The resulting DNA can be merged with the DNA genome of the host cell. The main enzyme responsible for synthesis of DNA from an RNA template is called reverse transcriptase.
Transcription factor
There are approximately 2600 proteins in the human genome that contain DNA-binding domains, and most of these are presumed to function as transcription factors, though other studies indicate it to be a smaller number. Therefore, approximately 10% of genes in the genome code for transcription factors, which makes this family the single largest family of human proteins. Furthermore, genes are often flanked by several binding sites for distinct transcription factors, and efficient expression of each of these genes requires the cooperative action of several different transcription factors (see, for example, hepatocyte nuclear factors). Hence, the combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development.
Transcriptional amplification
At the subset of genes expressed in a given cell, the transcribing activity of RNA Polymerase II results in mRNA production. Transcriptional amplification is specifically defined as the increase in per-cell abundance of this set of expressed mRNAs. Transcriptional amplification is caused by changes in the amount or activity of transcription-regulating proteins.
Primary transcript
R-loops are formed during transcription. An R-loop is a three-stranded nucleic acid structure containing a DNA-RNA hybrid region and an associated non-template single-stranded DNA. Actively transcribed regions of DNA often form R-loops that are vulnerable to DNA damage. Introns reduce R-loop formation and DNA damage in highly expressed yeast genes.
P53
p53 becomes activated in response to myriad stressors, including but not limited to DNA damage (induced by either UV, IR, or chemical agents such as hydrogen peroxide), oxidative stress, osmotic shock, ribonucleotide depletion, and deregulated oncogene expression. This activation is marked by two major events. First, the half-life of the p53 protein is increased drastically, leading to a quick accumulation of p53 in stressed cells. Second, a conformational change forces p53 to be activated as a transcription regulator in these cells. The critical event leading to the activation of p53 is the phosphorylation of its N-terminal domain. The N-terminal transcriptional activation domain contains a large number of phosphorylation sites and can be considered as the primary target for protein kinases transducing stress signals.
Eukaryotic transcription
Transcription is the process of copying genetic information stored in a DNA strand into a transportable complementary strand of RNA. Eukaryotic transcription takes place in the nucleus of the cell and proceeds in three sequential stages: initiation, elongation, and termination. The transcriptional machinery that catalyzes this complex reaction has at its core three multi-subunit RNA polymerases. RNA polymerase I is responsible for transcribing RNA that codes for genes that become structural components of the ribosome.
Protein coding genes are transcribed into messenger RNAs (mRNAs) that carry the information from DNA to the site of protein synthesis. Although mRNAs possess great diversity, they are not the most abundant RNA species made in the cell. The so-called non-coding RNAs account for the large majority of the transcriptional output of a cell. These non-coding RNAs perform a variety of important cellular functions.
Transcription (biology)
RNA polymerase, assisted by one or more general transcription factors, then unwinds approximately 14 base pairs of DNA to form an RNA polymerase-promoter "open complex". In the "open complex" the promoter DNA is partly unwound and single-stranded. The exposed, single-stranded DNA is referred to as the "transcription bubble."
Triple-stranded DNA
TFOs bind specifically to homopurine-homopyrimidine regions that are often common in promoter and intron sequences of genes influencing cell signaling. TFOs can inhibit transcription by binding with high specificity to the DNA helix, thereby blocking the binding and function of transcription factors for particular sequences. By using highly specific DNA segments to target TFO regions, expression of genes can be controlled. This application has novel implications in site-specific mutagenesis and gene therapy. In human prostate cancer cells, a transcription factor Ets2 is over-expressed and thought to drive forward the growth and survival of cells in such excess. Carbone et al. designed a sequence-specific TFO to the Ets2 promoter sequence that down-regulated the gene expression and led to a slowing of cell growth and cell death. Changxian et al. have also presented a TFO targeting the promoter sequence of bcl-2, a gene inhibiting apoptosis.
Transcriptor
On March 28, 2013, a team of bioengineers from Stanford University led by Drew Endy announced that they had created the biological equivalent of a transistor, which they named a "transcriptor". That is, they created a three-terminal device with a logic system that can control other components. The transcriptor regulates the flow of RNA polymerase across a strand of DNA using special combinations of enzymes to control movement. According to project member Jerome Bonnet, "The choice of enzymes is important. We have been careful to select enzymes that function in bacteria, fungi, plants and animals, so that bio-computers can be engineered within a variety of organisms."
Archaeal transcription factor B
As transcription is a process essential to cell survival and proliferation, there has been much study of the involved proteins. In bacteria and eukaryotes, proteins TFIIB and sigma factor are involved in the initiation of transcription, where they facilitate preinitiation complex formation and specific RNA Polymerase-DNA binding. The archaeal counterpart to these two proteins is TFB, which was first identified in the species "Pyrococcus woesei" in 1992. Since then, research has found that archaeal species must contain at least one copy of TFB to function, although some species may have multiple isoforms in their genome.
Signal transduction
Gene activations and metabolism alterations are examples of cellular responses to extracellular stimulation that require signal transduction. Gene activation leads to further cellular effects, since the products of responding genes include instigators of activation; transcription factors produced as a result of a signal transduction cascade can activate even more genes. Hence, an initial stimulus can trigger the expression of a large number of genes, leading to physiological events like the increased uptake of glucose from the blood stream and the migration of neutrophils to sites of infection. The set of genes and their activation order to certain stimuli is referred to as a genetic program.
Regulation of transcription in cancer
Generally, in progression to cancer, hundreds of genes are silenced or activated. Although silencing of some genes in cancers occurs by mutation, a large proportion of carcinogenic gene silencing is a result of altered DNA methylation (see DNA methylation in cancer). DNA methylation causing silencing in cancer typically occurs at multiple CpG sites in the CpG islands that are present in the promoters of protein coding genes.
Protein biosynthesis
In transcription an mRNA chain is generated, with one strand of the DNA double helix in the genome as a template. This strand is called the template strand. Transcription can be divided into 3 stages: initiation, elongation, and termination, each regulated by a large number of proteins such as transcription factors and coactivators that ensure that the correct gene is transcribed.
Regulation of gene expression
Regulation of transcription thus controls when transcription occurs and how much RNA is created. Transcription of a gene by RNA polymerase can be regulated by several mechanisms.
Specificity factors alter the specificity of RNA polymerase for a given promoter or set of promoters, making it more or less likely to bind to them (i.e., sigma factors used in prokaryotic transcription).
Repressors bind to the Operator, coding sequences on the DNA strand that are close to or overlapping the promoter region, impeding RNA polymerase's progress along the strand, thus impeding the expression of the gene.The image to the right demonstrates regulation by a repressor in the lac operon.
General transcription factors position RNA polymerase at the start of a protein-coding sequence and then release the polymerase to transcribe the mRNA.
Activators enhance the interaction between RNA polymerase and a particular promoter, encouraging the expression of the gene. Activators do this by increasing the attraction of RNA polymerase for the promoter, through interactions with subunits of the RNA polymerase or indirectly by changing the structure of the DNA.
Enhancers are sites on the DNA helix that are bound by activators in order to loop the DNA bringing a specific promoter to the initiation complex. Enhancers are much more common in eukaryotes than prokaryotes, where only a few examples exist (to date).
Silencers are regions of DNA sequences that, when bound by particular transcription factors, can silence expression of the gene.
Transcription (biology)
The "non"-template (sense) strand of DNA is called the coding strand, because its sequence is the same as the newly created RNA transcript (except for the substitution of uracil for thymine). This is the strand that is used by convention when presenting a DNA sequence.
Gene
Transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed. The mRNA acts as an intermediate between the DNA gene and its final protein product. The gene's DNA is used as a template to generate a complementary mRNA. The mRNA matches the sequence of the gene's DNA coding strand because it is synthesised as the complement of the template strand. Transcription is performed by an enzyme called an RNA polymerase, which reads the template strand in the 3' to 5' direction and synthesizes the RNA from 5' to 3'. To initiate transcription, the polymerase first recognizes and binds a promoter region of the gene. Thus, a major mechanism of gene regulation is the blocking or sequestering the promoter region, either by tight binding by repressor molecules that physically block the polymerase, or by organizing the DNA so that the promoter region is not accessible.
Transcription factories
It was previously thought that it was the relatively small RNA polymerase that moves along the comparatively larger DNA template during transcription. However, increasing evidence supports the notion that due to the tethering of a transcription factory to the nuclear matrix, it is in fact the large DNA template that is moved to accommodate RNA polymerisation. "In vitro" studies for example have shown that RNA polymerases attached to a surface are capable of both rotating the DNA template and threading it through the polymerase to start transcription; which indicates the capabilities of RNA polymerase to be a molecular motor. Chromosome Conformation Capture (3C) also supports the idea of the DNA template diffusing towards a stationary RNA polymerase.
Silencer (genetics)
In genetics, a silencer is a DNA sequence capable of binding transcription regulation factors, called repressors. DNA contains genes and provides the template to produce messenger RNA (mRNA). That mRNA is then translated into proteins. When a repressor protein binds to the silencer region of DNA, RNA polymerase is prevented from transcribing the DNA sequence into RNA. With transcription blocked, the translation of RNA into proteins is impossible. Thus, silencers prevent genes from being expressed as proteins.
Central dogma of molecular biology
Transcription is the process by which the information contained in a section of DNA is replicated in the form of a newly assembled piece of messenger RNA (mRNA). Enzymes facilitating the process include RNA polymerase and transcription factors. In eukaryotic cells the primary transcript is pre-mRNA. Pre-mRNA must be processed for translation to proceed. Processing includes the addition of a 5' cap and a poly-A tail to the pre-mRNA chain, followed by splicing. Alternative splicing occurs when appropriate, increasing the diversity of the proteins that any single mRNA can produce. The product of the entire transcription process (that began with the production of the pre-mRNA chain) is a mature mRNA chain.
Abortive initiation
For many years, the mechanism by which RNA polymerase moves along the DNA strand during abortive initiation remained elusive. It had been observed that RNA polymerase did not escape from the promoter during transcription initiation, so it was unknown how the enzyme could read the DNA strand to transcribe it without moving downstream. Within the last decade, studies have revealed that abortive initiation involves "DNA scrunching," in which RNA polymerase remains stationary while it unwinds and pulls downstream DNA into the transcription complex to pass the nucleotides through the polymerase active site, thereby transcribing the DNA without moving. This causes the unwound DNA to accumulate within the enzyme, hence the name DNA "scrunching". In abortive initiation, RNA polymerase re-winds and ejects the downstream portion of the unwound DNA, releasing the RNA, and reverting to the RNA polymerase-promoter open complex; in contrast, in productive initiation, RNA polymerase re-winds and ejects the upstream portion of the unwound DNA, breaking RNA polymerase-promoter interactions, escaping the promoter, and forming a transcription elongation complex.
Transcriptional regulation
Once a polymerase is successfully bound to a DNA template, it often requires the assistance of other proteins in order to leave the stable promoter complex and begin elongating the nascent RNA strand. This process is called promoter escape, and is another step at which regulatory elements can act to accelerate or slow the transcription process. Similarly, protein and nucleic acid factors can associate with the elongation complex and modulate the rate at which the polymerase moves along the DNA template.
Hormone receptor
Intracellular and nuclear receptors are a direct way for the cell to respond to internal changes and signals. Intracellular receptors are activated by hydrophobic ligands that pass through the cellular membrane. All nuclear receptors are very similar in structure, and are described with intrinsic transcriptional activity. Intrinsic transcriptional involves the three following domains: transcription-activating, DNA-binding, and ligand-binding. These domains and ligands are hydrophobic and are able to travel through the membrane. The movement of macromolecules and ligand molecules into the cell enables a complex transport system of intracellular signal transfers through different cellular environments until response is enabled. Nuclear receptors are a special class of intracellular receptor that specifically aid the needs of the cell to express certain genes. Nuclear receptors often bind directly to DNA by targeting specific DNA sequences in order to express or repress transcription of nearby genes.
Gene expression
The activity of transcription factors is further modulated by intracellular signals causing protein post-translational modification including phosphorylated, acetylated, or glycosylated. These changes influence a transcription factor's ability to bind, directly or indirectly, to promoter DNA, to recruit RNA polymerase, or to favor elongation of a newly synthesized RNA molecule.
Transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the right cell at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 2600 TFs in the human genome.
DNA
As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.
Transcription coregulator
Nuclear DNA is normally tightly wrapped around histones rendering the DNA inaccessible to the general transcription machinery and hence this tight association prevents transcription of DNA. At physiological pH, the phosphate component of the DNA backbone is deprotonated which gives DNA a net negative charge. Histones are rich in lysine residues which at physiological pH are protonated and therefore positively charged. The electrostatic attraction between these opposite charges is largely responsible for the tight binding of DNA to histones.
Heat shock protein 90kDa alpha (cytosolic), member A1
Transcription of the HSP90AA1 gene is currently understood to be induced by stress through binding of the master transcription factor (TF) HSF1 to the HSP90AA1 promoter However, several focused studies of the HSP90AA1 promoter along with extensive global analysis of the human genome indicate that various other transcription complexes regulate HSP90AA1 gene expression. Mammalian HSP90AA1 along with HSP90AB1 gene expression was first characterized in transformed mouse cells where it was shown that HSP90AB1 is constitutively expressed 2.5-fold higher than HSP90AA1 under normal conditions. However upon heat shock, HSP90AA1 expression increased 7.0-fold while HSP90AB1 increases only 4.5-fold. Detailed analysis of the HSP90AA1 promoter shows that there are 2 heat shock elements (HSE) within 1200 bp of the transcription start site. The distal HSE is required for heat shock induction and the proximal HSE functions as a permissive enhancer. This model is supported by ChIP-SEQ analysis of cells under normal conditions where HSF1 is found bound to the proximal HSE and not detected at the distal HSE. The proto-oncogene MYC is also found to induce HSP90AA1 gene expression and binds proximally to the TSS as verified by ChIP-SEQ. Depletion of Hsp90A expression indicates that HSP90AA1 is required for MYC-driven transformation. In breast cancer cells the growth hormone prolactin induces HSP90AA1 expression through STAT5. NF-κB or RELA also induces HSP90AA1 expression possibly explaining the pro-survival ability of NF-κB-driven transcription. Conversely, STAT1, the proto-tumor suppressor, is found to inhibit stress induced expression of HSP90AA1. In addition to these findings, ChIP-SEQ analysis of the human genome indicates that at least 85 unique TFs bind to the RNA polymerase II (POLR2A) footprints associated with the promoter regions that drive the expression of both HSP90AA1 transcript variants. This indicates that HSP90AA1 gene expression may be highly regulated and complex.
Inducer
For a gene to be expressed, its DNA sequence must be copied (in a process known as transcription) to make a smaller, mobile molecule called messenger RNA (mRNA), which carries the instructions for making a protein to the site where the protein is manufactured (in a process known as translation). Many different types of proteins can affect the level of gene expression by promoting or preventing transcription. In prokaryotes (such as bacteria), these proteins often act on a portion of DNA known as the operator at the beginning of the gene. The promoter is where RNA polymerase, the enzyme that copies the genetic sequence and synthesizes the mRNA, attaches to the DNA strand.
Some genes are modulated by activators, which have the opposite effect on gene expression as repressors. Inducers can also bind to activator proteins, allowing them to bind to the operator DNA where they promote RNA transcription.
Transcription factories
In genetics, transcription factories describe the discrete sites where transcription occurs in the nucleus. They were first discovered in 1993 and have been found to have structures analogous to replication factories, sites where replication also occurs in discrete sites. The factories contain an RNA polymerase (active or inactive) and the necessary transcription factors (activators and repressors) for transcription. Transcription factories containing RNA polymerase II are the most studied but factories can exist for RNA polymerase I and III; the nucleolus being seen as the prototype for transcription factories. It is possible to view them under both light and electron microscropy. The discovery of transcription factories has challenged the original view of how RNA polymerase interacts with the DNA polymer and it is thought that the presence of factories has important effects on gene regulation and nuclear structure.
Introduction to viruses
Transcription is the process where information in DNA, called the genetic code, is used to produce RNA copies called messenger RNA (mRNA). These migrate through the cell and carry the code to ribosomes where it is used to make proteins. This is called translation because the protein's amino acid structure is determined by the mRNA's code. Information is hence translated from the language of nucleic acids to the language of amino acids.
Transcription (journal)
Transcription is a scientific journal published by Taylor & Francis focusing on the subject of the transcription of DNA. Its stated aim is to publish "high-quality articles that provide novel insights, provocative questions, and new hypotheses into the expanding field of gene transcription".
Archaeal transcription factor B
Archaeal transcription factor B (ATFB or TFB) is one of several extrinsic transcription factors that guide the initiation of RNA transcription in organisms that fall under the domain of Archaea. It is homologous to eukaryotic TFIIB and, more distantly, to bacterial sigma factor. Like these proteins, it is involved in forming transcription preinitiation complexes. Its structure includes several conserved motifs which interact with DNA and other transcription factors, notably the single type of RNA polymerase that performs transcription in Archaea.
Primary transcript
Activation of RNA polymerase activity to produce primary transcripts is often controlled by sequences of DNA called enhancers. Transcription factors, proteins that bind to DNA elements to either activate or repress transcription, bind to enhancers and recruit enzymes that alter nucleosome components, causing DNA to be either more or less accessible to RNA polymerase. The unique combinations of either activating or inhibiting transcription factors that bind to enhancer DNA regions determine whether or not the gene that enhancer interacts with is activated for transcription or not. Activation of transcription depends on whether or not the transcription elongation complex, itself consisting of a variety of transcription factors, can induce RNA polymerase to dissociate from the Mediator complex that connects an enhancer region to the promoter.
General transcription factor
A transcription factor is a protein that binds to specific DNA sequences (enhancer or promoter), either alone or with other proteins in a complex, to control the rate of transcription of genetic information from DNA to messenger RNA by promoting (serving as an activator) or blocking (serving as a repressor) the recruitment of RNA polymerase. As a class of protein, general transcription factors bind to promoters along the DNA sequence or form a large transcription preinitiation complex to activate transcription. General transcription factors are necessary for transcription to occur.
Transcription factor
In eukaryotes, an important class of transcription factors called general transcription factors (GTFs) are necessary for transcription to occur. Many of these GTFs do not actually bind DNA, but rather are part of the large transcription preinitiation complex that interacts with RNA polymerase directly. The most common GTFs are TFIIA, TFIIB, TFIID (see also TATA binding protein), TFIIE, TFIIF, and TFIIH. The preinitiation complex binds to promoter regions of DNA upstream to the gene that they regulate.
Nucleosome
Studies in 2007 have catalogued nucleosome positions in yeast and shown that nucleosomes are depleted in promoter regions and origins of replication.
About 80% of the yeast genome appears to be covered by nucleosomes and the pattern of nucleosome positioning clearly relates to DNA regions that regulate transcription, regions that are transcribed and regions that initiate DNA replication. Most recently, a new study examined "dynamic changes" in nucleosome repositioning during a global transcriptional reprogramming event to elucidate the effects on nucleosome displacement during genome-wide transcriptional changes in yeast ("Saccharomyces cerevisiae"). The results suggested that nucleosomes that were localized to promoter regions are displaced in response to stress (like heat shock). In addition, the removal of nucleosomes usually corresponded to transcriptional activation and the replacement of nucleosomes usually corresponded to transcriptional repression, presumably because transcription factor binding sites became more or less accessible, respectively. In general, only one or two nucleosomes were repositioned at the promoter to effect these transcriptional changes. However, even in chromosomal regions that were not associated with transcriptional changes, nucleosome repositioning was observed, suggesting that the covering and uncovering of transcriptional DNA does not necessarily produce a transcriptional event. After transcription, the rDNA region has to protected from any damage, it suggested HMGB proteins play a major role in protecting the nucleosome free region.
Transcription (biology)
Mechanistically, promoter escape occurs through DNA scrunching, providing the energy needed to break interactions between RNA polymerase holoenzyme and the promoter.
Cell nucleus
In order to control which genes are being transcribed, the cell separates some transcription factor proteins responsible for regulating gene expression from physical access to the DNA until they are activated by other signaling pathways. This prevents even low levels of inappropriate gene expression. For example, in the case of NF-κB-controlled genes, which are involved in most inflammatory responses, transcription is induced in response to a signal pathway such as that initiated by the signaling molecule TNF-α, binds to a cell membrane receptor, resulting in the recruitment of signalling proteins, and eventually activating the transcription factor NF-κB. A nuclear localisation signal on the NF-κB protein allows it to be transported through the nuclear pore and into the nucleus, where it stimulates the transcription of the target genes.
Transcription factor
Gene duplications have played a crucial role in the evolution of species. This applies particularly to transcription factors. Once they occur as duplicates, accumulated mutations encoding for one copy can take place without negatively affecting the regulation of downstream targets. However, changes of the DNA binding specificities of the single-copy LEAFY transcription factor, which occurs in most land plants, have recently been elucidated. In that respect, a single-copy transcription factor can undergo a change of specificity through a promiscuous intermediate without losing function. Similar mechanisms have been proposed in the context of all alternative phylogenetic hypotheses, and the role of transcription factors in the evolution of all species.
Spongelab Interactive
Transcription Hero
is a game that is inspired by the popular Guitar Hero series. You play the role of RNA polymerase (the enzyme responsible for DNA transcription). As the DNA sequence scrolls towards the player on the screen, the player will need to transcribe it by pressing the corresponding keys on the guitar.
Post-transcriptional regulation
After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA binding protein (RBP) that control the various steps and rates cripts: events such as alternative splicing, nuclear degradation (exosome), processing, nuclear export (three alternative pathways), sequestration in P-bodies for storage or degradation and ultimately translation. These proteins achieve these events thanks to an RNA recognition motif (RRM) that binds a specific sequence or secondary structure of the transcripts, typically at the 5’ and 3’ UTR of the transcript. In short, the dsRNA sequences, which will be broken down into siRNA inside of the organism, will match up with the DNA causing the gene to shut down in every cell.
Protein biosynthesis
Transcription occurs in the cell nucleus, where the DNA is held and is never able to leave. The DNA structure of the cell is made up of two helixes made up of sugar and phosphate held together by hydrogen bonds between the bases of opposite strands. The sugar and the phosphate in each strand are joined together by stronger phosphodiester covalent bonds. The DNA is "unzipped" (disruption of hydrogen bonds between different single strands) by the enzyme helicase, leaving the single nucleotide chain open to be copied. RNA polymerase reads the DNA strand from the 3-prime (3') end to the 5-prime (5') end, while it synthesizes a single strand of messenger RNA in the 5'-to-3' direction. The general RNA structure is very similar to the DNA structure, but in RNA the nucleotide uracil takes the place that thymine occupies in DNA. The single strand of mRNA leaves the nucleus through nuclear pores, and migrates into the cytoplasm.
Transcription (biology)
Transcription begins with the binding of RNA polymerase, together with one or more general transcription factors, to a specific DNA sequence referred to as a "promoter" to form an RNA polymerase-promoter "closed complex". In the "closed complex" the promoter DNA is still fully double-stranded.