An oestrogen-receptor-alpha-bound human chromatin interactome.

An oestrogen-receptor-alpha-bound human chromatin interactome.
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DOI:
10.1038/nature08497
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发表时间:
2009-11-05
期刊:
影响因子:
64.8
通讯作者:
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中科院分区:
综合性期刊1区
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基因组被组织成高水平的三维结构,并且被长基因组距离分开的DNA元件可以在功能上相互作用。许多转录因子结合到远离基因启动子的调控DNA元件上。虽然远端结合位点已被证明通过在几个位点的长距离染色质相互作用来调节转录,但染色质相互作用及其对转录调节的影响尚未以全基因组的方式进行研究。因此,我们开发了双端标签测序染色质相互作用分析(ChIA-PET)技术,对染色质相互作用进行从头检测,并全面绘制了人类基因组中雌激素受体α(ERα)结合的染色质相互作用网络。我们发现,大多数高置信度的远程ERα结合位点通过长距离染色质相互作用锚定在基因启动子上,这表明ERα通过广泛的染色质循环将基因聚集在一起进行协调的转录调控。我们认为染色质相互作用是哺乳动物基因组转录调控的主要机制。
Genomes are organized into high-level 3-dimensional structures, and DNA elements separated by long genomic distances could functionally interact. Many transcription factors bind to regulatory DNA elements distant from gene promoters. While distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Therefore, we developed Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) for de novo detection of global chromatin interactions, and comprehensively mapped the chromatin interaction network bound by oestrogen receptor α (ERα) in the human genome. We found that most high-confidence remote ERα binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ERα functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.
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