Discovery and Annotation of Functional Chromatin Signatures in the Human Genome
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{"title"=>"Discovery and annotation of functional chromatin signatures in the human genome", "type"=>"journal", "authors"=>[{"first_name"=>"Gary", "last_name"=>"Hon", "scopus_author_id"=>"16021627800"}, {"first_name"=>"Wei", "last_name"=>"Wang", "scopus_author_id"=>"57191738639"}, {"first_name"=>"Bing", "last_name"=>"Ren", "scopus_author_id"=>"7102054727"}], "year"=>2009, "source"=>"PLoS Computational Biology", "identifiers"=>{"scopus"=>"2-s2.0-73449092184", "doi"=>"10.1371/journal.pcbi.1000566", "sgr"=>"73449092184", "isbn"=>"1553-7358 (Electronic)\\n1553-734X (Linking)", "pmid"=>"19918365", "issn"=>"1553734X", "pui"=>"358053175"}, "id"=>"21776058-ec1f-30ff-a37e-e90899c709a5", "abstract"=>"Transcriptional regulation in human cells is a complex process involving a multitude of regulatory elements encoded by the genome. Recent studies have shown that distinct chromatin signatures mark a variety of functional genomic elements and that subtle variations of these signatures mark elements with different functions. To identify novel chromatin signatures in the human genome, we apply a de novo pattern-finding algorithm to genome-wide maps of histone modifications. We recover previously known chromatin signatures associated with promoters and enhancers. We also observe several chromatin signatures with strong enrichment of H3K36me3 marking exons. Closer examination reveals that H3K36me3 is found on well-positioned nucleosomes at exon 5' ends, and that this modification is a global mark of exon expression that also correlates with alternative splicing. Additionally, we observe strong enrichment of H2BK5me1 and H4K20me1 at highly expressed exons near the 5' end, in contrast to the opposite distribution of H3K36me3-marked exons. Finally, we also recover frequently occurring chromatin signatures displaying enrichment of repressive histone modifications. These signatures mark distinct repeat sequences and are associated with distinct modes of gene repression. Together, these results highlight the rich information embedded in the human epigenome and underscore its value in studying gene regulation.", "link"=>"http://www.mendeley.com/research/discovery-annotation-functional-chromatin-signatures-human-genome", "reader_count"=>232, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>24, "Researcher"=>62, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>78, "Student > Postgraduate"=>5, "Other"=>4, "Student > Master"=>18, "Student > Bachelor"=>12, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>18}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>24, "Researcher"=>62, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>78, "Student > Postgraduate"=>5, "Other"=>4, "Student > Master"=>18, "Student > Bachelor"=>12, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>18}, "reader_count_by_subject_area"=>{"Unspecified"=>9, "Agricultural and Biological Sciences"=>153, "Chemistry"=>1, "Computer Science"=>14, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>29, "Mathematics"=>3, "Medicine and Dentistry"=>14, "Neuroscience"=>1, "Physics and Astronomy"=>2, "Psychology"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>14}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Psychology"=>{"Psychology"=>1}, "Mathematics"=>{"Mathematics"=>3}, "Unspecified"=>{"Unspecified"=>9}, "Engineering"=>{"Engineering"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>153}, "Computer Science"=>{"Computer Science"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>29}}, "reader_count_by_country"=>{"United States"=>14, "United Kingdom"=>5, "Portugal"=>1, "Switzerland"=>1, "Spain"=>2, "Greece"=>1, "Sweden"=>2, "Netherlands"=>1, "China"=>1, "Brazil"=>2, "Denmark"=>1, "Italy"=>3, "Mexico"=>1, "Chile"=>1, "Germany"=>3}, "group_count"=>14}

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  • {"files"=>["https://ndownloader.figshare.com/files/877192"], "description"=>"<p>(A) Shown is a heat-map representing the enrichment of various modifications and factors in a 5-kb region surrounding the top third expressed exons. The exons are separated into (top) first exons and (bottom) non-first exons, and are then sorted by distance from the transcription start site. Non-first exons are further subcategorized into early, middle, and late exons. (B) The average profiles for (left) H2BK5me1, (middle) H3K36me3, and (right) H4K20me1 for first, early, middle, and late exons.</p>", "links"=>[], "tags"=>["h4k20me1"], "article_id"=>547656, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H2BK5me1_and_H4K20me1_mark_early_exons_/547656", "title"=>"H2BK5me1 and H4K20me1 mark early exons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-13 02:07:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/876941"], "description"=>"<p>(A) The top panel is a heat map of H3K36me3 enrichment at all human exons, sorted by exonic expression (right). The bottom panel is the average H3K36me3 enrichment profile of the lowest, middle, and highest third of expressed exons from the top panel. The distribution of H3K36me3 reads within ±500 bp of exon (B) 5′ ends and (C) 3′ ends of the top 50% expressed exons in the human genome. In red are reads on the sense strand in the direction of transcription, and in green are anti-sense reads. A schematic of a positioned a nucleosome is shown. (D–E) As in (B–C), but focusing on expressed exons longer than 500 bp.</p>", "links"=>[], "tags"=>["marks", "exon", "ends"], "article_id"=>547405, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H3K36me3_marks_exon_5_8242_ends_and_is_a_global_mark_of_expression_/547405", "title"=>"H3K36me3 marks exon 5′ ends and is a global mark of expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-13 02:03:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/877301"], "description"=>"<p>(A) The percentage of loci in U5 and U6 within 1-kb to an evolutionarily conserved PhastCons element. (B) The average percentage of bases ±1 kb around each locus that are masked by RepeatMasker. (C–D) The number of repeat elements within ±1 kb of each locus in (C) U5 and (D) U6. Black indicates the observed value while grey indicates the expected value over random sites. The error bars indicate ±1 standard deviation. LTR, long terminal repeat; simple, simple repeat.</p>", "links"=>[], "tags"=>["u6", "sequences"], "article_id"=>547759, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.g006", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_U5_and_U6_mark_distinct_sequences_of_the_genome_/547759", "title"=>"U5 and U6 mark distinct sequences of the genome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-13 02:09:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/877082"], "description"=>"<p>The number of H3K36me3 reads per kilobase for exons near alternatively spliced cassette exons that are (A) spliced in or (B) spliced out. A cassette exon is defined to be spliced in if the difference in expression between it and its immediate upstream and downstream exons is less than 0.5 on a log2 scale. A cassette exon is defined to be spliced out if both upstream and downstream exons are at least 2-fold more expressed (1.0 on a log2 scale).</p>", "links"=>[], "tags"=>["enrichment", "correlates"], "article_id"=>547539, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H3K36me3_enrichment_correlates_with_alternative_splicing_/547539", "title"=>"H3K36me3 enrichment correlates with alternative splicing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-13 02:05:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/434674", "https://ndownloader.figshare.com/files/434716", "https://ndownloader.figshare.com/files/434742", "https://ndownloader.figshare.com/files/434779", "https://ndownloader.figshare.com/files/434821", "https://ndownloader.figshare.com/files/434858", "https://ndownloader.figshare.com/files/434904", "https://ndownloader.figshare.com/files/434959", "https://ndownloader.figshare.com/files/435008", "https://ndownloader.figshare.com/files/435058", "https://ndownloader.figshare.com/files/435089", "https://ndownloader.figshare.com/files/435151", "https://ndownloader.figshare.com/files/435173", "https://ndownloader.figshare.com/files/435194", "https://ndownloader.figshare.com/files/435212", "https://ndownloader.figshare.com/files/435230", "https://ndownloader.figshare.com/files/435252", "https://ndownloader.figshare.com/files/435275"], "description"=>"<div><p>Transcriptional regulation in human cells is a complex process involving a multitude of regulatory elements encoded by the genome. Recent studies have shown that distinct chromatin signatures mark a variety of functional genomic elements and that subtle variations of these signatures mark elements with different functions. To identify novel chromatin signatures in the human genome, we apply a <em>de novo</em> pattern-finding algorithm to genome-wide maps of histone modifications. We recover previously known chromatin signatures associated with promoters and enhancers. We also observe several chromatin signatures with strong enrichment of H3K36me3 marking exons. Closer examination reveals that H3K36me3 is found on well-positioned nucleosomes at exon 5′ ends, and that this modification is a global mark of exon expression that also correlates with alternative splicing. Additionally, we observe strong enrichment of H2BK5me1 and H4K20me1 at highly expressed exons near the 5′ end, in contrast to the opposite distribution of H3K36me3-marked exons. Finally, we also recover frequently occurring chromatin signatures displaying enrichment of repressive histone modifications. These signatures mark distinct repeat sequences and are associated with distinct modes of gene repression. Together, these results highlight the rich information embedded in the human epigenome and underscore its value in studying gene regulation.</p></div>", "links"=>[], "tags"=>["annotation", "chromatin", "signatures", "genome"], "article_id"=>145750, "categories"=>["Genetics", "Medicine", "Cancer"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1000566.s001", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s002", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s003", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s004", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s005", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s006", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s007", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s008", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s009", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s010", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s011", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s012", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s013", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s014", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s015", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s016", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s017", "https://dx.doi.org/10.1371/journal.pcbi.1000566.s018"], "stats"=>{"downloads"=>15, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Discovery_and_Annotation_of_Functional_Chromatin_Signatures_in_the_Human_Genome/145750", "title"=>"Discovery and Annotation of Functional Chromatin Signatures in the Human Genome", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-11-13 01:35:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/877475"], "description"=>"<p>Summary of chromatin signatures U1–7.</p>", "links"=>[], "tags"=>["chromatin", "signatures"], "article_id"=>547928, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_chromatin_signatures_U1_8211_7_/547928", "title"=>"Summary of chromatin signatures U1–7.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-11-13 02:12:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/877370"], "description"=>"<p>(A) Enrichment of U5 and U6 loci as a function of expression for genes in the same domain. We counted the number of U5 and U6 loci within the CTCF-defined domains containing human promoters, assessed enrichment as compared to that expected over random sites, and averaged over a 1000-promoter sliding window to create each profile. The signed rank p-value is indicated. (B) The percentage each cluster within lamina-associated domains, previously mapped in Tig3 human lung fibroblasts (black), as compared to random sites (grey). The error bars indicate ±1 standard deviation.</p>", "links"=>[], "tags"=>["u6", "domains"], "article_id"=>547833, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.g007", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_U5_and_U6_mark_distinct_expression_domains_of_the_genome_/547833", "title"=>"U5 and U6 mark distinct expression domains of the genome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-13 02:10:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/877439"], "description"=>"<p>* P(CpG) is the hypergeometric probability of finding more CpG-marked promoters than observed, as compared to the background distribution of all promoters. ** Selected Gene Ontology terms from the Biological Processes ontology significantly enriched with Benjamini-corrected p-value of 0.001. Abbreviations: dev, development; proc, process.</p>", "links"=>[], "tags"=>["promoter", "chromatin", "signatures"], "article_id"=>547898, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_promoter_chromatin_signatures_P1_8211_14_/547898", "title"=>"Summary of promoter chromatin signatures P1–14.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-11-13 02:11:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/876775"], "description"=>"<p>We identified 50,183 genomic loci with strong ChIP enrichment of histone modifications but distal to promoters, gene 3′ ends, DNase I hypersensitive sites, CTCF binding sites, and predicted enhancers. Applying ChromaSig to these loci reveals seven clusters U1–7 spanning 47,874 loci. The heat map represents the enrichment of H2AZ, 20 histone modifications, CTCF, and RNA polymerase II in the 10-kb region surrounding each locus. To organize these clusters visually, we performed hierarchical clustering on the average profiles of each ChromaSig cluster, using a Pearson correlation distance metric (left).</p>", "links"=>[], "tags"=>["chromatin", "signatures", "spanning", "genomic", "loci", "distal"], "article_id"=>547226, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.g002", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distinct_chromatin_signatures_spanning_genomic_loci_distal_to_known_regulatory_elements_/547226", "title"=>"Distinct chromatin signatures spanning genomic loci distal to known regulatory elements.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-13 02:00:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/876580"], "description"=>"<p>(left) Applying ChromaSig to the histone modifications near 20,389 Refseq promoters recovers 14 frequently-occurring chromatin signatures spanning 18,533 promoters. The heat map represents the enrichment of H2AZ, 20 histone modifications, CTCF, and RNA polymerase II in the 10-kb region surrounding each promoter. To organize these clusters visually, we performed hierarchical clustering on the average profiles using a Pearson correlation distance metric. (right) Gene expression data for CD4+ T cells measured from a previous study <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000566#pcbi.1000566-Crawford1\" target=\"_blank\">[14]</a>, and re-visualized here for the different classes of promoters. Shown are the distributions of gene expression level over promoters with different chromatin signatures. Red horizontal lines indicate the median, the box extends to the lower and upper quartiles, the whiskers extend to 1.5 times the inter-quartile range, and red “+” symbols are outliers.</p>", "links"=>[], "tags"=>["chromatin", "signatures", "spanning", "refseq"], "article_id"=>547038, "categories"=>["Genetics", "Medicine", "Infectious Diseases"], "users"=>["Gary Hon", "Wei Wang", "Bing Ren"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000566.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distinct_chromatin_signatures_spanning_Refseq_promoters_/547038", "title"=>"Distinct chromatin signatures spanning Refseq promoters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-13 01:57:18"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"18", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}

Relative Metric

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