Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding.
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.
Robertson
A Gordon
AG
BC Cancer Agency Genome Sciences Centre, Vancouver, Canada.
Bilenky
Mikhail
M
Tam
Angela
A
Zhao
Yongjun
Y
Zeng
Thomas
T
Thiessen
Nina
N
Cezard
Timothee
T
Fejes
Anthony P
AP
Wederell
Elizabeth D
ED
Cullum
Rebecca
R
Euskirchen
Ghia
G
Krzywinski
Martin
M
Birol
Inanc
I
Snyder
Michael
M
Hoodless
Pamela A
PA
Hirst
Martin
M
Marra
Marco A
MA
Jones
Steven J M
SJ
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*
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
Mol Cell. 2002 Dec;10(6):1467-77
12504020
Nat Genet. 2008 Jul;40(7):897-903
18552846
J Cell Biochem. 2005 Apr 1;94(5):890-8
15696541
Nucleic Acids Res. 2008 Aug;36(14):4549-64
18611952
Nat Genet. 2007 Mar;39(3):311-8
17277777
Cell. 2007 Mar 23;128(6):1231-45
17382889
Cell. 2008 Jan 25;132(2):311-22
18243105
Nature. 2007 Jun 14;447(7146):799-816
17571346
Bioinformatics. 2006 May 1;22(9):1036-46
16500937
Biochem Cell Biol. 2003 Jun;81(3):241-51
12897858
Curr Opin Genet Dev. 2008 Apr;18(2):159-68
18281209
Biophys J. 2004 Dec;87(6):4021-35
15465864
Genomics. 1988 Apr;2(3):231-9
3294162
Curr Opin Genet Dev. 2008 Apr;18(2):109-15
18339538
Trends Biochem Sci. 2005 Nov;30(11):593-9
16126390
Cell. 2007 May 18;129(4):823-37
17512414
Biochem Pharmacol. 2004 Sep 15;68(6):1145-55
15313412
Cell. 2008 Jun 13;133(6):1106-17
18555785
Biochem Cell Biol. 2007 Aug;85(4):435-43
17713579
J Interferon Cytokine Res. 2005 Dec;25(12):733-44
16375601
Nucleic Acids Res. 2008 Jan;36(Database issue):D88-92
18073188
Bioinformatics. 2008 Jul 1;24(13):i24-31
18586720
PLoS Biol. 2008 Feb;6(2):e27
18271625
Nat Methods. 2007 Aug;4(8):651-7
17558387
Bioinformatics. 2008 Aug 1;24(15):1729-30
18599518
Nucleic Acids Res. 2004 Jun 03;32(10):3040-52
15178741