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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >G9a selectively represses a class of late-replicating genes at the nuclear periphery
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G9a selectively represses a class of late-replicating genes at the nuclear periphery

机译:G9a在核外围选择性抑制一类晚期复制基因

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摘要

We have investigated the role of the histone methyltransferase G9a in the establishment of silent nuclear compartments. Following conditional knockout of the G9a methyltransferase in mouse ESCs, 167 genes were significantly up-regulated, and no genes were strongly down-regulated. A partially overlapping set of 119 genes were up-regulated after differentiation of G9a-depleted cells to neural precursors. Promoters of these G9a-repressed genes were AT rich and H3K9me2 enriched but H3K4me3 depleted and were not highly DNA methylated. Representative genes were found to be close to the nuclear periphery, which was significantly enriched for G9a-depen-dent H3K9me2. Strikingly, although 73% of total genes were early replicating, more than 71 % of G9a-repressed genes were late replicating, and a strong correlation was found between H3K9me2 and late replication. However, G9a loss did not significantly affect sub-nuclear position or replication timing of any non-pericentric regions of the genome, nor did it affect programmed changes in replication timing that accompany differentiation. We conclude that G9a is a gatekeeper for a specific set of genes localized within the late replicating nuclear periphery.
机译:我们已经研究了组蛋白甲基转移酶G9a在建立无声核区室中的作用。在小鼠ESC中有条件敲除G9a甲基转移酶后,167个基因被显着上调,而没有基因被强烈下调。 G9a耗尽的细胞分化为神经前体后,一组119个基因的部分重叠被上调。这些G9a阻遏基因的启动子富含AT,H3K9me2富集,但H3K4me3耗尽,且DNA甲基化程度不高。发现代表性基因接近核外围,其显着富集了G9a-依赖型H3K9me2。令人惊讶的是,尽管总基因中有73%处于早期复制状态,但超过71%的G9a抑制基因处于晚期复制状态,并且在H3K9me2与晚期复制之间存在着很强的相关性。但是,G9a的丢失不会显着影响基因组中任何非外周区域的亚核位置或复制时机,也不会影响伴随分化的复制时机的程序性变化。我们得出的结论是,G9a是位于晚期复制核外围的一组特定基因的网守。

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  • 作者单位

    Department of Biological Science, Florida State University, Tallahassee, FL 32306 Cancer Center Research Institute, 666-2 Nitona, Chuo, Chiba 260-8717, Japan;

    Department of Biological Science, Florida State University, Tallahassee, FL 32306;

    Department of Biological Science, Florida State University, Tallahassee, FL 32306;

    Department of Biological Science, Florida State University, Tallahassee, FL 32306;

    Department of Biological Science, Florida State University, Tallahassee, FL 32306;

    Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan;

    Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan;

    Department of Biological Science, Florida State University, Tallahassee, FL 32306;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    histone methylation; nucleus; replication timing; transcription;

    机译:组蛋白甲基化核;复制时间;抄写;

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