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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genome-wide Studies Highlight Indirect Links Between Human Replication Origins And Gene Regulation
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Genome-wide Studies Highlight Indirect Links Between Human Replication Origins And Gene Regulation

机译：全基因组研究突出了人类复制起源与基因调控之间的间接联系

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摘要

To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are evo-lutionarily conserved, and half of them map within or near CpG islands. Most of the origins overlap transcriptional regulatory elements, providing further evidence of a connection with gene regulation. Moreover, we identify c-JUN and c-FOS as important regulators of origin selection. Half of the identified replication initiation sites do not have an open chromatin configuration, showing the absence of a direct link with gene regulation. Replication timing analyses coupled with our origin mapping suggest that a relatively strict origin-timing program regulates the replication of the human genome.
机译：为了深入了解复制起始的调控，我们系统地沿HeLa细胞中1％的人类基因组复制了复制起点。我们确定了283个起源，比以前知道的多10倍。起源密度与基因组景观密切相关，在富含GC的区域中成簇的起源紧密排列，而在缺乏GC的大区域中没有起源。起源序列在进化上是保守的，其中一半位于CpG岛内或附近。大多数起源都与转录调控元件重叠，从而提供了与基因调控有关的进一步证据。此外，我们确定c-JUN和c-FOS是起源选择的重要调节剂。一半已鉴定的复制起始位点不具有开放的染色质构型，表明不存在与基因调控的直接联系。复制时间分析以及我们的原点定位图表明，相对严格的原点定时程序可调节人类基因组的复制。

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