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哺乳动物染色体中CpG岛处DNA复制的起始

Initiation of DNA replication at CpG islands in mammalian chromosomes.

作者信息

Delgado S, Gómez M, Bird A, Antequera F

机构信息

Instituto de Microbiología Bioquímica, CSIC/Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007-Salamanca, Spain.

出版信息

EMBO J. 1998 Apr 15;17(8):2426-35. doi: 10.1093/emboj/17.8.2426.

Abstract

CpG islands are G+C-rich regions approximately 1 kb long that are free of methylation and contain the promoters of many mammalian genes. Analysis of in vivo replication intermediates at three hamster genes and one human gene showed that the CpG island regions, but not their flanks, were present in very short nascent strands, suggesting that they are replication origins (ORIs). CpG island-like fragments were enriched in a population of short nascent strands from human erythroleukaemic cells, suggesting that islands constitute a significant fraction of endogenous ORIs. Correspondingly, bulk CpG islands were found to replicate coordinately early in S phase. Our results imply that CpG islands are initiation sites for both transcription and DNA replication, and may represent genomic footprints of replication initiation.

摘要

CpG岛是富含G+C的区域,长度约为1 kb,无甲基化,包含许多哺乳动物基因的启动子。对三个仓鼠基因和一个人类基因的体内复制中间体进行分析表明,CpG岛区域而非其侧翼存在于非常短的新生链中,这表明它们是复制起点(ORIs)。在人类红白血病细胞的短新生链群体中,类似CpG岛的片段得到富集,这表明这些岛构成了内源性ORIs的很大一部分。相应地,大量CpG岛在S期早期进行协同复制。我们的结果表明,CpG岛是转录和DNA复制的起始位点,可能代表复制起始的基因组印记。

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