title: Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding.
abstract: We characterized the relationship of H3K4me1 and H3K4me3 at distal and proximal regulatory elements by comparing ChIP-seq profiles for these histone modifications and for two functionally different transcription factors: STAT1 in the immortalized HeLa S3 cell line, with and without interferon-gamma (IFNG) stimulation; and FOXA2 in mouse adult liver tissue. In unstimulated and stimulated HeLa cells, respectively, we determined approximately 270,000 and approximately 301,000 H3K4me1-enriched regions, and approximately 54,500 and approximately 76,100 H3K4me3-enriched regions. In mouse adult liver, we determined approximately 227,000 and approximately 34,800 H3K4me1 and H3K4me3 regions. Seventy-five percent of the approximately 70,300 STAT1 binding sites in stimulated HeLa cells and 87% of the approximately 11,000 FOXA2 sites in mouse liver were distal to known gene TSS; in both cell types, approximately 83% of these distal sites were associated with at least one of the two histone modifications, and H3K4me1 was associated with over 96% of marked distal sites. After filtering against predicted transcription start sites, 50% of approximately 26,800 marked distal IFNG-stimulated STAT1 binding sites, but 95% of approximately 5800 marked distal FOXA2 sites, were associated with H3K4me1 only. Results for HeLa cells generated additional insights into transcriptional regulation involving STAT1. STAT1 binding was associated with 25% of all H3K4me1 regions in stimulated HeLa cells, suggesting that a single transcription factor can interact with an unexpectedly large fraction of regulatory regions. Strikingly, for a large majority of the locations of stimulated STAT1 binding, the dominant H3K4me1/me3 combinations were established before activation, suggesting mechanisms independent of IFNG stimulation and high-affinity STAT1 binding.
authors.affiliation: BC Cancer Agency Genome Sciences Centre, Vancouver, Canada.
authors.forename: A Gordon
authors.initials: AG
authors.lastname: Robertson
authors.forename: Mikhail
authors.initials: M
authors.lastname: Bilenky
authors.forename: Angela
authors.initials: A
authors.lastname: Tam
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeng
authors.forename: Nina
authors.initials: N
authors.lastname: Thiessen
authors.forename: Timothee
authors.initials: T
authors.lastname: Cezard
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Fejes
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Wederell
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cullum
authors.forename: Ghia
authors.initials: G
authors.lastname: Euskirchen
authors.forename: Martin
authors.initials: M
authors.lastname: Krzywinski
authors.forename: Inanc
authors.initials: I
authors.lastname: Birol
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Hoodless
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002461:Cell Line, Transformed; D047369:Chromatin Immunoprecipitation; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D006367:HeLa Cells; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C496503:Foxa2 protein, mouse; D006657:Histones; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D007371:Interferon-gamma; D008239:Lysine
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