Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding
Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding
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DOI：
10.1101/gr.078519.108
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发表时间：
2008-12-01
期刊：
影响因子：
7
通讯作者：
Jones, Steven J. M.
中科院分区：
文献类型：
--
作者：
Robertson, A. Gordon;Bilenky, Mikhail;Jones, Steven J. M.
我们通过比较这些组蛋白修饰和两个功能不同的转录因子的芯片序列谱来表征H3K4me1和H3K4me3在远端和近端调节元件的关系：永生化HeLa S3细胞系中的STAT1，在有和没有干扰素-γ(IFNG)刺激的情况下；以及在小鼠成年肝组织中的FOXA2。在未刺激和刺激的HeLa细胞中，我们分别测定了类似于27万和类似于301,000个H3K4me1富集区，类似于54,500和类似于76,100个H3K4me3富集区。在小鼠成年肝脏中，我们检测到类似于227,000和34,800个H3K4me1和H3K4me3区域。在受刺激的HeLa细胞和小鼠肝脏中，75%的类似于70,300个STAT1结合位点和87%的类似于11,000个FOXA2结合位点位于已知基因TSS的远端；在这两种细胞类型中，接近83%的这些远端结合位点至少与两个组蛋白修饰中的一个相关，而H3K4me1与超过96%的标记远端结合位点相关。筛选预测的转录起始点后，26,800个标记的远端IFNG刺激的STAT1结合位点中有50%与H3K4me1相关，而5800个标记的FOXA2远端结合位点中的95%仅与H3K4me1相关。对HeLa细胞的结果为涉及STAT1的转录调控提供了额外的见解。在受刺激的HeLa细胞中，STAT1结合与所有H3K4me1区域的25%相关，这表明单个转录因子可以与出人意料的大部分调节区相互作用。值得注意的是，对于大多数受刺激的STAT1结合位置，主要的H3K4me1/ME3组合在激活前就已经建立，这表明其机制独立于IFNG刺激和高亲和力的STAT1结合。
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 similar to 270,000 and similar to 301,000 H3K4me1-enriched regions, and similar to 54,500 and similar to 76,100 H3K4me3-enriched regions. In mouse adult liver, we determined similar to 227,000 and similar to 34,800 H3K4me1 and H3K4me3 regions. Seventy-five percent of the similar to 70,300 STAT1 binding sites in stimulated HeLa cells and 87% of the similar to 11,000 FOXA2 sites in mouse liver were distal to known gene TSS; in both cell types, similar to 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 similar to 26,800 marked distal IFNG-stimulated STAT1 binding sites, but 95% of similar to 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.