DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements.

DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements.
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DNase I 超敏感外显子与启动子和远端调控元件共定位。

DOI:
10.1038/ng.2677
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发表时间:
2013-08
期刊:
影响因子:
30.8
通讯作者:
Stamatoyannopoulos, John A.
Stamatoyannopoulos, John A.
中科院分区:
生物学1区
文献类型:
--
作者:
Mercer, Tim R.;Edwards, Stacey L.;Clark, Michael B.;Neph, Shane J.;Wang, Hao;Stergachis, Andrew B.;John, Sam;Sandstrom, Richard;Li, Guoliang;Sandhu, Kuljeet S.;Ruan, Yijun;Nielsen, Lars K.;Mattick, John S.;Stamatoyannopoulos, John A.

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基因的精确拼接赋予人类基因组巨大的转录复杂性。大多数基因剪接发生共转录,允许表观遗传修饰影响剪接结果。在这里,我们表明,选择外显子区域内划分的三维结构的人类基因组。我们确定了一个子集的外显子,表现出DNase I超敏反应,并伴随着'幻影'信号染色质免疫沉淀和测序(ChIP-seq),导致与近端启动子或增强子结合因子的交联。通过染色质相互作用分析证实了ChIP-seq对结构特征的捕获,染色质相互作用分析解析了靠近同源启动子折叠外显子的局部基因内环,同时排除了插入的内含子序列。外显子与启动子和增强子的这些相互作用对于选择性剪接事件是富集的,这种效应反映在细胞类型特异性外显子周DNA酶I超敏性模式中。总的来说,我们的研究结果连接本地基因组拓扑结构,染色质结构和顺式调控景观与人类转录复杂性的产生,共转录剪接。
The precise splicing of genes confers an enormous transcriptional complexity to the human genome. The majority of gene splicing occurs cotranscriptionally, permitting epigenetic modifications to affect splicing outcomes. Here we show that select exonic regions are demarcated within the three-dimensional structure of the human genome. We identify a subset of exons that exhibit DNase I hypersensitivity and are accompanied by ‘phantom’ signals in chromatin immunoprecipitation and sequencing (ChIP-seq) that result from cross-linking with proximal promoter- or enhancer-bound factors. The capture of structural features by ChIP-seq is confirmed by chromatin interaction analysis that resolves local intragenic loops that fold exons close to cognate promoters while excluding intervening intronic sequences. These interactions of exons with promoters and enhancers are enriched for alternative splicing events, an effect reflected in cell type-specific periexonic DNase I hypersensitivity patterns. Collectively, our results connect local genome topography, chromatin structure and cis-regulatory landscapes with the generation of human transcriptional complexity by cotranscriptional splicing.
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