The patterns of histone modifications in the vicinity of transcription factor binding sites in human lymphoblastoid cell lines.
The patterns of histone modifications in the vicinity of transcription factor binding sites in human lymphoblastoid cell lines.
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DOI：
10.1371/journal.pone.0060002
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Nie Y;Liu H;Sun X
转录因子(TF)与特定DNA序列的结合是转录调控的基本步骤，高度依赖于染色质结构背景，而染色质结构背景可能会受到特定的组蛋白修饰和变体(称为组蛋白标记)的影响。缺乏数百种转录因子的全球结合图谱意味着以前的研究主要集中在几个特定转录因子结合位点的组蛋白标记上。因此，我们研究了11个组蛋白标记，分别基于人类淋巴母细胞系中164个和34个TF的计算推断和实验确定的TF结合位点(TFBs)。对于H_2A.Z、H3K4甲基化和H3K27和H3K9的乙酰化，标记模式在TFBS富集区周围的600bp区域呈现双峰分布和强烈的成对相关性，表明这些标记主要共存于Tf位点附近的两个核小体中。TFS与核小体竞争访问大多数结合部位的DNA，导致双峰分布，这是Tf结合的组蛋白标记的共同特征。标记H3K79me2在TFBS的一侧呈单峰分布，信号延伸到4000bp，显示出较长的距离模式。有趣的是，H4K20me1、H3K27me3、H3K36me3和H3K9me3在TFBs周围弥散分布，而H3K9me3的丰度较低，呈单峰分布，提示某些TFs可能与核小体DNA结合。此外，H3K36me3和H3K9me3的不对称分布表明，抑制子可能在一个方向上建立了抑制染色质结构，从而抑制基因的表达。总之，本研究证实了与Tf结合相关的组蛋白标记的范围，以及这些标记在结合部位周围的共同特征。这些发现对未来对调控因素的分析具有表观遗传学意义。
Transcription factor (TF) binding at specific DNA sequences is the fundamental step in transcriptional regulation and is highly dependent on the chromatin structure context, which may be affected by specific histone modifications and variants, known as histone marks. The lack of a global binding map for hundreds of TFs means that previous studies have focused mainly on histone marks at binding sites for several specific TFs. We therefore studied 11 histone marks around computationally-inferred and experimentally-determined TF binding sites (TFBSs), based on 164 and 34 TFs, respectively, in human lymphoblastoid cell lines. For H2A.Z, methylation of H3K4, and acetylation of H3K27 and H3K9, the mark patterns exhibited bimodal distributions and strong pairwise correlations in the 600-bp region around enriched TFBSs, suggesting that these marks mainly coexist within the two nucleosomes proximal to the TF sites. TFs competing with nucleosomes to access DNA at most binding sites, contributes to the bimodal distribution, which is a common feature of histone marks for TF binding. Mark H3K79me2 showed a unimodal distribution on one side of TFBSs and the signals extended up to 4000 bp, indicating a longer-distance pattern. Interestingly, H4K20me1, H3K27me3, H3K36me3 and H3K9me3, which were more diffuse and less enriched surrounding TFBSs, showed unimodal distributions around the enriched TFBSs, suggesting that some TFs may bind to nucleosomal DNA. Besides, asymmetrical distributions of H3K36me3 and H3K9me3 indicated that repressors might establish a repressive chromatin structure in one direction to repress gene expression. In conclusion, this study demonstrated the ranges of histone marks associated with TF binding, and the common features of these marks around the binding sites. These findings have epigenetic implications for future analysis of regulatory elements.
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