Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs
Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs
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DOI：
10.1038/nsmb.2339
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发表时间：
2012-08-01
影响因子：
16.8
通讯作者：
Lemaitre, Jean-Marc
中科院分区：
文献类型：
--
作者：
Besnard, Emilie;Babied, Amelie;Lemaitre, Jean-Marc
DNA复制受到高度调控，确保在每个细胞周期中忠实地遗传遗传信息。在后生动物中，这一过程始于数千个DNA复制起始点，这些起始点的细胞类型特定的分布和使用情况知之甚少。我们使用新生短链的深度测序详尽地绘制了人类细胞中复制起点的全基因组位置，并确定了比我们预期多十倍的起点位置；这些位置中的大多数在四个不同的人类细胞系中保守。此外，我们确定了一个共识的G-四链形成DNA基序，该基序可以预测DNA复制起点在人类细胞中的位置，考虑到它们的分布、使用效率和时机。最后，我们发现了一种特定于细胞类型的可重编程的细胞同一性签名，它是通过保守起始点位置的特定效率来揭示的，而不是通过选择特定于细胞类型的起始子集来揭示的。
DNA replication is highly regulated, ensuring faithful inheritance of genetic information through each cell cycle. In metazoans, this process is initiated at many thousands of DNA replication origins whose cell type-specific distribution and usage are poorly understood. We exhaustively mapped the genome-wide location of replication origins in human cells using deep sequencing of short nascent strands and identified ten times more origin positions than we expected; most of these positions were conserved in four different human cell lines. Furthermore, we identified a consensus G-quadruplex-forming DNA motif that can predict the position of DNA replication origins in human cells, accounting for their distribution, usage efficiency and timing. Finally, we discovered a cell type-specific reprogrammable signature of cell identity that was revealed by specific efficiencies of conserved origin positions and not by the selection of cell type-specific subsets of origins.