eukaryotic nuclear dna , along with a variety of proteins , is organized and packaged into a complex structure called chromatin .
the basic , repeating unit of chromatin is the nucleosome which consists of the dna duplex wound approximately twice around an octamer consisting of two copies each of the four core histones h2a , h2b , h3 and h4 .
nucleosomes undergo further compaction to form the distinct structures seen as chromosomes ( 1 ) .
the function of chromatin is to maintain a restrictive ground state wherein the dna is inaccessible to the transcriptional machinery but is accessible to protein complexes capable of remodeling chromatin locally to allow transcription initiation .
additionally , chromatin has a pivotal role in a number of dna - associated processes , e.g. replication ( 2 ) , repair ( 3,4 ) , kinetochore and centromere formation ( 5 ) .
histones are ideally suited for this role , as both the histone tails and globular domains are subjected to a variety of posttranslational modifications such as acetylation , methylation , phosphorylation , ubiquitination , sumoylation , adp ribosylation , deimination and proline isomerization ( 6 ) .
nucleosomes are remodeled by the action of at least five classes of atp - dependent chromatin remodelers ( 7 ) .
there are many other facets to chromatin biology and chromatin remodeling which involve a variety of proteins associated with nucleosome assembly and disassembly ( 8,9 ) , dna methylation ( 10,11 ) and more , e.g. histone variants ( 12 ) and the involvement of rnai components in heterochromatic gene silencing ( 13 ) .
chromatin biology is complicated and multifaceted and a comprehensive review of this subject is beyond the scope of this article .
in addition to the limited number of reviews cited above , readers are referred to a special issue of cell , volume 128 ( 2007 ) ,  epigenetics and chromatin organization , which provides a series of excellent reviews on different aspects of chromatin biology and epigenetics .
the chromdb public database ( http://www.chromdb.org ) serves as a repository for chromatin - related proteins .
chromdb was initiated as a national science foundation plant genome project database and focused on arabidopsis thaliana and zea mays ( maize ) .
the database was populated using saccharomyces cerevisiae and animal chromatin - associated proteins as blast queries to search the nearly completed arabidopsis genome and the maize est collection to identify corresponding plant homologs .
chromdb has grown from several hundred plant proteins to over 7000 proteins representing over 30 organisms ( 7474 proteins total : 3328 plants , 1779 animals , 2143 fungi , 167 stramenopiles , 57 protists ) .
currently , the database focuses on chromatin - related proteins that are conserved widely across eukaryotic species .
our main research interest lies in the analysis of the evolution of the plant chromatin proteome . to facilitate this study and to make the database applicable to all researchers and educators interested in chromatin biology ,
we strive to organize chromdb data in a straightforward and comparative manner and provide users with a variety of tools to visualize sequence information and to extract data by way of user - generated customized reports .
our goal is to make information on chromatin - associated proteins readily accessible despite the relative complexity of the processes .
the chromdb database was initiated in 2000 as a project database for a national science foundation plant genome research program grant ( dbi-9975930 ; r. jorgensen , pi ) which focused on the identification and functional analysis of z. mays ( maize ) and a. thaliana genes that contribute to chromatin - based control of gene expression .
one aspect of the aforementioned project was to produce and analyze rnai lines for a set of arabidopsis and maize chromatin - associated genes and display the results at a public database .
chromdb has evolved from a project database to a community database with renewed funding from the plant genome research program ( nsf dbi-0421679 ; pi napoli ) .
the web interface is built in html::mason , taking advantage of mason 's ability to embed perl within html .
perl modules have been developed to access data based on user queries and pass this information back to the web pages for mason to interpret and display the results .
the database is a mysql relational database running in a unix background with the schema developed to account for the type of data used and generated at the website .
genomic - based sequences are limited to plant genomes [ a. thaliana , oryza sativa ( japonica cultivar- and indica cultivar - groups ) , medicago truncatula , populus trichocarpa , physcomitrella patens ( moss ) and z. mays ] and algal and diatom genomes ( chlamydomonas reinhardtii , ostreococcus lucimarinus and phaeodactylum tricornutum ) .
the plant genomes are highlighted on the side toolbar on the chromdb homepage ( shown on the left side in figure 1 ) .
other important plant species are included in the database as transcript - based sequences which are derived from est contigs or singlets . the use of est contigs results in partial sequences especially for larger proteins .
for example , 200 transcript - based sequences are included in the database for hordeum vulgare ( barley ) but only 36% of these transcripts represent the entire , predicted coding sequence .
partial protein sequences , usually protein domains or the c - termini , are used as blast queries when identifying est contigs . the use of a limited span of protein , rather than the entire sequence , limits redundancy that could result from the inclusion of multiple , non - overlapping contigs representing different regions of the same transcript .
transcript - based plant sequences are converted to genome - based as sequencing projects produce sufficient data to make a conversion worthwhile .
for example , maize is being converted from transcript - based to genomic - based due to the rapid accumulation of sequence data from large - scale maize genome sequencing projects . 

figure 1.a screen shot of a gene record page along with the side tool bar for accessing database searching , tools , reports and viewers .
a screen shot of a gene record page along with the side tool bar for accessing database searching , tools , reports and viewers .
chromdb does not display whole chromosomes ; thus for genomic - based organisms , the genomic sequence is limited to a span of nucleotides containing the predicted transcript splice model and 5 and 3 untranslated regions .
plant sequences are obtained from a variety of sources , e.g. ncbi databases ( http://www.ncbi.nlm.nih.gov/ ) , the department of energy joint genome institute ( http://www.jgi.doe.gov/ ) , the arabidopsis information resource ( http://www.arabidopsis.org/ ) ; the j. craig venter institute [ http://www.tigr.org/ , formally the institute for genomic research ( tigr ) ] and plantgdb ( http://www.plantgdb.org/ ) .
all plant sequences are curated by chromdb staff members to provide the best transcript models . in many cases ,
we have derived our own transcript models from genomic sequences using fgnesh or fgenesh+ licensed from softberry ( http://www.softberry.com ) .
we make use of multiple sequence alignments to analyze plant proteins and correct models where biological support of the model ( cdna sequences ) is not available .
important animal and fungal model organisms , such as homo sapiens , drosophila melanogaster and s. cerevisiae , are available as transcript - based sequences and are obtained from the ncbi reference sequence ( refseq ) collection ( http://www.ncbi.nlm.nih.gov/refseq/ ) .
we focus on sequenced genomes and do not derive est contigs for non - plant organisms .
these transcripts are rarely curated by chromdb staff , except for predicted transcript models that need substantial improvement as indicated by multiple sequence analysis and only when refseq accessions affect the quality of a phylogenetic tree .
all database sequences are assigned a chromdb i d ( identifier ) which denotes both the transcript and the protein .
these identifiers , as well as formal gene names , loci and aliases are included in the database and can be used to search for gene records .
an explanation of the chromdb identifiers is provided in the help manual under section iv entitled chromdb identifiers .
chromdb identifiers are not gene names and are not intended to take the place of recognized formal names ; these are database identifiers and serve as one level of database organization .
one of the more difficult aspects of the database relates to providing a straightforward hierarchical organization of the range of chromdb protein groups associated with chromatin remodeling .
this difficulty relates to the complexity of the full range of proteins associated with chromatin remodeling .
there are over 90 protein groups displayed at chromdb ; however , they can be grouped into parent categories reflecting different functional aspects of chromatin biology , as shown in supplementary table 1 .
the next , lower level of organization is the individual protein groups , i.e. the three- to five - letter designations .
the more complex groups such as the chr proteins ( swi / snf chromatin remodeling atpase super family ) can be broken down further into distinct phylogenetic groups , e.g. snf2 , chd1 , rad16 ( 14,15 ) .
this protein group classification scheme forms the basis for advanced searching and generating reports , two of our important database tools . a full description of the hierarchy is provided in the supplemental data table 1 .
however , we warn readers that these groups may change slightly by the time this manuscript is published , as we continue to find new ways to organize data in a straightforward manner that allows for ease of navigation through the website .
the major divisions of protein groups are as follows : histones and histone linker proteins , nucleosome organization ( includes assembly and displacement ) , histone modifications , histone modification binding - proteins , modified - histone - binding proteins , dna modifying proteins , non - histone dna - binding proteins , rnai components and chromosome dynamics .
the contents of the database can be searched , compared , and visualized using a variety of search functions , viewers and report tools .
two search options are provided , a limited  quick search text box and a menu - driven 
the  quick search text box is located at the top of every webpage and accepts single entries for gene names , either the chromdb i d , the formal gene name , an alternative alias or a locus . in those cases where the same formal gene name is used for multiple organisms , a list is generated showing each gene name and organism , as well as the chromdb i d .
for example , the argonaute gene designated as ago1 is used for homologous genes in arabidopsis , d. melanogaster , and schizocaccharomyces pombe and a quick search using ago1 will bring up all three entries . additionally , this text box accepts an organism name ( either the scientific or common name ) or an ncbi accession .
advanced search is available from the link on the side menu shown in figure 1 .
this link brings up a menu - driven format that allows the user to customize a search in a variety of ways using three different criteria : organisms , protein groups and the type of report .
for the organisms , the default is an alphabetical list of scientific names , and a link is provided to switch to a taxon classification ( e.g. plants , animals , fungi ) .
for the protein group selection , the default is the functional groups shown in supplementary table 1 , and a link is provided to display an alphabetical list of all protein groups .
alternatively , a link is provided that displays a text box for entering a list of gene names as well as the report selection .
the gene record page is the central navigation portal for accessing information relating to each database gene .
regular users of the database will notice a new look to the chromdb website and the gene record pages .
new additions are ncbi entrez gene link ( if available ) , a chromdb taxon description , a drop - down menu of fasta formatted sequences , the organism / sequence classification ( transcript- or genomic - based ) , and a thumbnail view of the gbrowse display .
figure 1 shows a screen shot of the summary or default page of a gene record page .
the tabular format at the top of the gene record page provides access for additional information such as  decorated sequences , ncbi accessions and the gbrowse display .
two more tabs , titled expression and rnai , will appear for some maize and arabidopsis genes , as we have retained the rna gels and rnai information from the previous grant .
more information regarding each tab can be found on the help page at the website ( http://www.chromdb.org/help/genepage.html ) .
chromdb uses the gmod tool , gbrowse ( 16 ) as an individual gene - based visualization tool and not as a genome wide or chromosome visualization tool . for genomic - based organisms ,
the gbrowse view is based on the genomic sequence and the display includes the transcript splice model , protein domains ( aligned against the transcript model ) and ncbi accessions .
the inclusion of the protein domains aligned to exons is useful in discerning the effect of alternate transcript splicing on protein domain structure .
each individual plant can have specialized tracks , for example arabidopsis displays have a track for agrobacterium t - dna insertion events ( 17 ; http://signal.salk.edu/ ) for transcript - based plant organisms , the gbrowse display is based on the transcript and tracks include ncbi accessions and protein domains . for non - plant organisms ,
the gbrowse display is limited to the transcript , protein domains and the refseq accession .
in addition to similarity searching , this tool is useful in determining if a gene is present in the database .
users can select the standard blast programs as well as preset databases such as plants , animals , or fungi . on the results page ,
each match is linked back to that gene 's gene record page where more information can be obtained about that gene .
there is a link on the homepage on the left tool bar and within the web pages .
for example , each plant genome page has a list of appropriate links , e.g. tair ( the arabidopsis information resource ) , among others , for a. thaliana , the craig venter institute ( tigr ) for a number of organisms .
part of our mission is to provide the community with the means to make comparative analyses of chromatin - associated proteins among a diverse group of organisms .
the links for these comparative tools and viewers are provided on the side tool bar on each web page .
most of these features use the same menu - driven interface discussed above for the  advanced search feature . examples of these features are : the ability to form fasta files ( entire sequence or a protein domain ) and viewers for pfam and smart protein domains and exon structure ( see supplementary data for examples of the protein and exon viewers ) .
a full description of all chromdb tools will not be listed here , but the contents can be seen in the side tool bar in figure 1 .
information about the selection menus and the tools can be found on the general help page ( http://www.chromdb.org/help/help.html ) .
genomic - based sequences are limited to plant genomes [ a. thaliana , oryza sativa ( japonica cultivar- and indica cultivar - groups ) , medicago truncatula , populus trichocarpa , physcomitrella patens ( moss ) and z. mays ] and algal and diatom genomes ( chlamydomonas reinhardtii , ostreococcus lucimarinus and phaeodactylum tricornutum ) .
the plant genomes are highlighted on the side toolbar on the chromdb homepage ( shown on the left side in figure 1 ) .
other important plant species are included in the database as transcript - based sequences which are derived from est contigs or singlets . the use of est contigs results in partial sequences especially for larger proteins .
for example , 200 transcript - based sequences are included in the database for hordeum vulgare ( barley ) but only 36% of these transcripts represent the entire , predicted coding sequence .
partial protein sequences , usually protein domains or the c - termini , are used as blast queries when identifying est contigs . the use of a limited span of protein , rather than the entire sequence , limits redundancy that could result from the inclusion of multiple , non - overlapping contigs representing different regions of the same transcript .
transcript - based plant sequences are converted to genome - based as sequencing projects produce sufficient data to make a conversion worthwhile .
for example , maize is being converted from transcript - based to genomic - based due to the rapid accumulation of sequence data from large - scale maize genome sequencing projects . 

figure 1.a screen shot of a gene record page along with the side tool bar for accessing database searching , tools , reports and viewers .
a screen shot of a gene record page along with the side tool bar for accessing database searching , tools , reports and viewers .
chromdb does not display whole chromosomes ; thus for genomic - based organisms , the genomic sequence is limited to a span of nucleotides containing the predicted transcript splice model and 5 and 3 untranslated regions .
plant sequences are obtained from a variety of sources , e.g. ncbi databases ( http://www.ncbi.nlm.nih.gov/ ) , the department of energy joint genome institute ( http://www.jgi.doe.gov/ ) , the arabidopsis information resource ( http://www.arabidopsis.org/ ) ; the j. craig venter institute [ http://www.tigr.org/ , formally the institute for genomic research ( tigr ) ] and plantgdb ( http://www.plantgdb.org/ ) .
all plant sequences are curated by chromdb staff members to provide the best transcript models . in many cases ,
we have derived our own transcript models from genomic sequences using fgnesh or fgenesh+ licensed from softberry ( http://www.softberry.com ) .
we make use of multiple sequence alignments to analyze plant proteins and correct models where biological support of the model ( cdna sequences ) is not available .
important animal and fungal model organisms , such as homo sapiens , drosophila melanogaster and s. cerevisiae , are available as transcript - based sequences and are obtained from the ncbi reference sequence ( refseq ) collection ( http://www.ncbi.nlm.nih.gov/refseq/ ) .
we focus on sequenced genomes and do not derive est contigs for non - plant organisms .
these transcripts are rarely curated by chromdb staff , except for predicted transcript models that need substantial improvement as indicated by multiple sequence analysis and only when refseq accessions affect the quality of a phylogenetic tree .
all database sequences are assigned a chromdb i d ( identifier ) which denotes both the transcript and the protein .
these identifiers , as well as formal gene names , loci and aliases are included in the database and can be used to search for gene records .
an explanation of the chromdb identifiers is provided in the help manual under section iv entitled chromdb identifiers .
chromdb identifiers are not gene names and are not intended to take the place of recognized formal names ; these are database identifiers and serve as one level of database organization .
one of the more difficult aspects of the database relates to providing a straightforward hierarchical organization of the range of chromdb protein groups associated with chromatin remodeling .
this difficulty relates to the complexity of the full range of proteins associated with chromatin remodeling .
there are over 90 protein groups displayed at chromdb ; however , they can be grouped into parent categories reflecting different functional aspects of chromatin biology , as shown in supplementary table 1 .
the next , lower level of organization is the individual protein groups , i.e. the three- to five - letter designations .
the more complex groups such as the chr proteins ( swi / snf chromatin remodeling atpase super family ) can be broken down further into distinct phylogenetic groups , e.g. snf2 , chd1 , rad16 ( 14,15 ) .
this protein group classification scheme forms the basis for advanced searching and generating reports , two of our important database tools . a full description of the hierarchy is provided in the supplemental data table 1 .
however , we warn readers that these groups may change slightly by the time this manuscript is published , as we continue to find new ways to organize data in a straightforward manner that allows for ease of navigation through the website
. the major divisions of protein groups are as follows : histones and histone linker proteins , nucleosome organization ( includes assembly and displacement ) , histone modifications , histone modification binding - proteins , modified - histone - binding proteins , dna modifying proteins , non - histone dna - binding proteins , rnai components and chromosome dynamics .
the contents of the database can be searched , compared , and visualized using a variety of search functions , viewers and report tools .
two search options are provided , a limited  quick search text box and a menu - driven 
the  quick search text box is located at the top of every webpage and accepts single entries for gene names , either the chromdb i d , the formal gene name , an alternative alias or a locus . in those cases where the same formal gene name is used for multiple organisms , a list is generated showing each gene name and organism , as well as the chromdb i d .
for example , the argonaute gene designated as ago1 is used for homologous genes in arabidopsis , d. melanogaster , and schizocaccharomyces pombe and a quick search using ago1 will bring up all three entries . additionally , this text box accepts an organism name ( either the scientific or common name ) or an ncbi accession
advanced search is available from the link on the side menu shown in figure 1 .
this link brings up a menu - driven format that allows the user to customize a search in a variety of ways using three different criteria : organisms , protein groups and the type of report .
for the organisms , the default is an alphabetical list of scientific names , and a link is provided to switch to a taxon classification ( e.g. plants , animals , fungi ) . for the protein group selection ,
the default is the functional groups shown in supplementary table 1 , and a link is provided to display an alphabetical list of all protein groups .
alternatively , a link is provided that displays a text box for entering a list of gene names as well as the report selection .
the gene record page is the central navigation portal for accessing information relating to each database gene .
regular users of the database will notice a new look to the chromdb website and the gene record pages .
new additions are ncbi entrez gene link ( if available ) , a chromdb taxon description , a drop - down menu of fasta formatted sequences , the organism / sequence classification ( transcript- or genomic - based ) , and a thumbnail view of the gbrowse display .
figure 1 shows a screen shot of the summary or default page of a gene record page .
the tabular format at the top of the gene record page provides access for additional information such as  decorated sequences , ncbi accessions and the gbrowse display .
two more tabs , titled expression and rnai , will appear for some maize and arabidopsis genes , as we have retained the rna gels and rnai information from the previous grant .
more information regarding each tab can be found on the help page at the website ( http://www.chromdb.org/help/genepage.html ) .
chromdb uses the gmod tool , gbrowse ( 16 ) as an individual gene - based visualization tool and not as a genome wide or chromosome visualization tool . for genomic - based organisms ,
the gbrowse view is based on the genomic sequence and the display includes the transcript splice model , protein domains ( aligned against the transcript model ) and ncbi accessions .
the inclusion of the protein domains aligned to exons is useful in discerning the effect of alternate transcript splicing on protein domain structure .
each individual plant can have specialized tracks , for example arabidopsis displays have a track for agrobacterium t - dna insertion events ( 17 ; http://signal.salk.edu/ ) for transcript - based plant organisms , the gbrowse display is based on the transcript and tracks include ncbi accessions and protein domains . for non - plant organisms ,
the gbrowse display is limited to the transcript , protein domains and the refseq accession .
in addition to similarity searching , this tool is useful in determining if a gene is present in the database .
users can select the standard blast programs as well as preset databases such as plants , animals , or fungi . on the results page ,
each match is linked back to that gene 's gene record page where more information can be obtained about that gene .
there is a link on the homepage on the left tool bar and within the web pages .
for example , each plant genome page has a list of appropriate links , e.g. tair ( the arabidopsis information resource ) , among others , for a. thaliana , the craig venter institute ( tigr ) for a number of organisms .
part of our mission is to provide the community with the means to make comparative analyses of chromatin - associated proteins among a diverse group of organisms .
the links for these comparative tools and viewers are provided on the side tool bar on each web page .
most of these features use the same menu - driven interface discussed above for the  advanced search feature . examples of these features are : the ability to form fasta files ( entire sequence or a protein domain ) and viewers for pfam and smart protein domains and exon structure ( see supplementary data for examples of the protein and exon viewers ) .
a full description of all chromdb tools will not be listed here , but the contents can be seen in the side tool bar in figure 1 .
information about the selection menus and the tools can be found on the general help page ( http://www.chromdb.org/help/help.html ) .
we have not included data on the number of genes for each organism in this article , as those numbers will change by the publication date .
we add new protein groups to reflect new discoveries in the literature , and we continue to devise new tools to enable users to extract information from mysql tables .
new datasets ( organisms and protein groups ) and tools are prepared at our development site , and weekly updates are run to sync production and development to reflect data releases .
a link is provided on the homepage so users can access a list of updated contents .
a phylogenetic classification scheme will be introduced in the future to further subdivide protein groups .
we will post multiple sequence alignments , as well as the phylogenetic trees , in support of the classifications .
the chromdb website changes continually , both in content and appearance , as we strive to present users with a comprehensive database of chromatin - associated proteins for an ever - increasing number of organisms , and as we endeavor to find new ways to display the data in a straightforward and comparative manner .
 the chromdb website ( http://www.chromdb.org ) displays chromatin - associated proteins , including rnai - associated proteins , for a broad range of organisms . 
 our primary focus is to display sets of highly curated plant genes predicted to encode proteins associated with chromatin remodeling . 
 our intent is to make this intensively curated sequence information available to the research and teaching communities in support of comparative analyses toward understanding the chromatin proteome in plants , especially in important crop species such as corn and rice . 
 model animal and fungal proteins are included in the database to facilitate a complete , comparative analysis of the chromatin proteome and to make the database applicable to all chromatin researchers and educators . 
 chromatin biology and chromatin remodeling are complex processes involving a multitude of proteins that regulate the dynamic changes in chromatin structure which either repress or activate transcription . 
 we strive to organize chromdb data in a straightforward and comparative manner to help users understand the complement of proteins involved in packaging dna into chromatin . 
INTRODUCTION
DATABASE DESCRIPTION
Database contents
Database protein groups
Database access and interface
Comparative tools
FUTURE DIRECTION
SUPPLEMENTARY DATA