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

Genome Research, Vol. 18, No. 12. (3 December 2008), pp. 1906-1917.

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chip-seq chromatin human

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10.1101/gr.078519.108 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 â¼270,000 and â¼301,000 H3K4me1-enriched regions, and â¼54,500 and â¼76,100 H3K4me3-enriched regions. In mouse adult liver, we determined â¼227,000 and â¼34,800 H3K4me1 and H3K4me3 regions. Seventy-five percent of the â¼70,300 STAT1 binding sites in stimulated HeLa cells and 87% of the â¼11,000 FOXA2 sites in mouse liver were distal to known gene TSS; in both cell types, â¼83% 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 â¼26,800 marked distal IFNG-stimulated STAT1 binding sites, but 95% of â¼5800 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.


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