Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding

Autor: Timothee Cezard, Angela Tam, Michael Snyder, Marco A. Marra, Elizabeth D. Wederell, Pamela A. Hoodless, Mikhail Bilenky, Martin Krzywinski, Martin Hirst, Steven J.M. Jones, Ghia Euskirchen, A. Gordon Robertson, Nina Thiessen, Rebecca Cullum, Inanc Birol, Anthony P. Fejes, Thomas Zeng, Yongjun Zhao
Rok vydání: 2008
Předmět:
Zdroj: Genome Research. 18:1906-1917
ISSN: 1088-9051
DOI: 10.1101/gr.078519.108
Popis: 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.
Databáze: OpenAIRE