• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >lincRNAs act in the circuitry controlling pluripotency and differentiation
【24h】

lincRNAs act in the circuitry controlling pluripotency and differentiation

机译：lincRNA在控制多能性和分化的电路中起作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.%哺乳动物基因组编码很多类别的RNA，这些RNA不与蛋白编码(信使)RNA、tRNAs或rRNAs对应。这些所谓的非编码RNA是否有一个功能，如果有，该功能是什么，仍是一个有待回答的问题。Lander及其同事对小鼠胚胎干细胞中的“长基因间非编码RNA”(lincRNA)进行了系统性的“功能丧失”分析。
机译：尽管已经在哺乳动物中鉴定出数千种大型的基因间非编码RNA（lincRNA），但几乎没有功能上的特征，这引起了人们对其生物学作用的争论。为了解决这个问题，我们对小鼠胚胎干（ES）细胞中表达的大多数lincRNA进行了功能丧失研究，并表征了对基因表达的影响。在这里，我们显示敲低lincRNAs对基因表达模式具有重大影响，可与敲除著名的ES细胞调节剂相媲美。值得注意的是，lincRNA主要影响反式基因的表达。击倒数十个lincRNA会导致退出多能状态或谱系承诺程序上调。我们将lincRNAs整合到ES细胞的分子电路中，并显示lincRNA基因受关键转录因子调控，并且lincRNA转录物与多种染色质调控蛋白结合，从而影响共享的基因表达程序。在一起，结果表明lincRNA在控制ES细胞状态的电路中起着关键作用。％哺乳动物基因组编码很多类别的RNA，这些RNA不与蛋白编码（信使）RNA，tRNA或rRNA对应。兰德及其同事对小鼠植入干细胞中的“长基因间非编码RNA”（lincRNA）进行了系统性的“功能”的确认，是否有一个功能，如果有，该功能是什么，仍是一个有待回答的问题。丧失”分析。

著录项

  • 来源
    《Nature》 |2011年第7364期|p.295-300a25|共7页
  • 作者

    Mitchell Guttman; Julie Donaghey; Bryce W. Carey; Manuel Garber; Jennifer K. Grenier; Glen Munson; Geneva Young; Anne Bergstrom Lucas; Robert Ach; Laurakay Bruhn; Xiaoping Yang; Ido Amit; Alexander Meissner; Aviv Regev; John L. Rinn; David E. Root; Eric S. Lander;

  • 作者单位

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    Genomics Research and Development, Agilent Technologies, Santa Clara, California 95051,USA;

    Genomics Research and Development, Agilent Technologies, Santa Clara, California 95051,USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MITand Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号