Discovery and annotation of functional chromatin signatures in the human genome.
Discovery and annotation of functional chromatin signatures in the human genome.
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DOI：
10.1371/journal.pcbi.1000566
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发表时间：
2009-11
影响因子：
4.3
通讯作者：
Ren B
中科院分区：
文献类型：
--
作者：
Hon G;Wang W;Ren B
人类细胞中的转录调控是一个复杂的过程，涉及基因组编码的众多调控元件。近期研究表明，不同的染色质特征标记了多种功能性基因组元件，并且这些特征的细微变化标记了具有不同功能的元件。为了在人类基因组中识别新的染色质特征，我们将一种从头模式发现算法应用于全基因组的组蛋白修饰图谱。我们找回了先前已知的与启动子和增强子相关的染色质特征。我们还观察到几种染色质特征，其中H3K36me3强烈富集于外显子。进一步研究发现，H3K36me3存在于外显子5′端定位良好的核小体上，并且这种修饰是外显子表达的一种全局标记，也与可变剪接相关。此外，我们观察到在靠近5′端的高表达外显子处H2BK5me1和H4K20me1强烈富集，这与H3K36me3标记的外显子的分布情况相反。最后，我们还找回了频繁出现的显示抑制性组蛋白修饰富集的染色质特征。这些特征标记了不同的重复序列，并与不同的基因抑制模式相关。总之，这些结果凸显了人类表观基因组中蕴含的丰富信息，并强调了其在研究基因调控方面的价值。
近期研究观察到组蛋白尾部可以通过多种方式被修饰。通过分析21种组蛋白修饰，我们试图确定与不同类别的调控元件相关的常见特征是什么，以及它们是否标记具有不同功能的位置。实际上，在启动子处，我们识别出了许多不同的特征，每种特征都与不同类别的表达和功能性基因相关。我们还观察到了几种意想不到的标记外显子的特征，这些特征与外显子的表达直接相关。最后，我们找回了许多由两种不同的抑制性修饰标记的位置，并表明它们标记了与不同基因抑制模式相关的不同重复元件群体。总之，这些结果凸显了人类表观基因组中蕴含的丰富信息，并强调了其在研究基因调控方面的价值。
Transcriptional regulation in human cells is a complex process involving a multitude of regulatory elements encoded by the genome. Recent studies have shown that distinct chromatin signatures mark a variety of functional genomic elements and that subtle variations of these signatures mark elements with different functions. To identify novel chromatin signatures in the human genome, we apply a de novo pattern-finding algorithm to genome-wide maps of histone modifications. We recover previously known chromatin signatures associated with promoters and enhancers. We also observe several chromatin signatures with strong enrichment of H3K36me3 marking exons. Closer examination reveals that H3K36me3 is found on well-positioned nucleosomes at exon 5′ ends, and that this modification is a global mark of exon expression that also correlates with alternative splicing. Additionally, we observe strong enrichment of H2BK5me1 and H4K20me1 at highly expressed exons near the 5′ end, in contrast to the opposite distribution of H3K36me3-marked exons. Finally, we also recover frequently occurring chromatin signatures displaying enrichment of repressive histone modifications. These signatures mark distinct repeat sequences and are associated with distinct modes of gene repression. Together, these results highlight the rich information embedded in the human epigenome and underscore its value in studying gene regulation. Recent studies have observed that histone tails can be modified in a variety of ways. Analyzing a collection of 21 histone modifications, we attempted to determine what common signatures are associated with different classes of regulatory elements and whether they mark places of distinct function. Indeed, at promoters, we identified a number of distinct signatures, each associated with a different class of expressed and functional genes. We also observed several unexpected signatures marking exons that directly correlate with the expression of exons. Finally, we recovered many places marked by two distinct repressive modifications, and showed that they mark distinct populations of repetitive elements associated with distinct modes of gene repression. Together, these results highlight the rich information embedded in the human epigenome and underscore its value in studying gene regulation.
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通讯作者：
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