• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Regulation of RNA polymerase Ⅱ activation by histone acetylation in single living cells
【24h】

Regulation of RNA polymerase Ⅱ activation by histone acetylation in single living cells

机译：组蛋白乙酰化作用在单个活细胞中调控RNA聚合酶Ⅱ的活化

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

组蛋白的转录后修饰在基因调控中起重要作用,但这些标记是否是转录或在下游所造成后果的活跃调控因子仍不清楚。在这项研究中,Tim Stasevich等人利用荧光显微镜方法以高时间分辨率对单个活细胞中组蛋白乙酰化与“RNA聚合酶Ⅱ”活性之间的动态互动进行了调查。组蛋白H3 Lys27在一个活跃基因位点上的乙酰化会增强对一个转录激活因子的吸引,加速“RNA聚合酶Ⅱ”从启动到伸长的转变。这些发现表明,组蛋白乙酰化对转录激发的两个不同步骤有一个因果效应。%In eukaryotic cells, post-translational histone modifications have an important role in gene regulation. Starting with early work on histone acetylation, a variety of residue-specific modifications have now been linked to RNA polymerase Ⅱ (RNAP2) activity, but it remains unclear if these markers are active regulators of transcription or just passive byproducts. This is because studies have traditionally relied on fixed cell populations, meaning temporal resolution is limited to minutes at best, and correlated factors may not actually be present in the same cell at the same time. Complementary approaches are therefore needed to probe the dynamic interplay of histone modifications and RNAP2 with higher temporal resolution in single living cells. Here we address this problem by developing a system to track residue-specific histone modifications and RNAP2 phosphorylation in living cells by fluorescence microscopy. This increases temporal resolution to the tens-of-seconds range. Our single-cell analysis reveals histone H3 lysine-27 acetylation at a gene locus can alter downstream transcription kinetics by as much as 50%, affecting two temporally separate events. First acetylation enhances the search kinetics of transcriptional activators, and later the acetylation accelerates the transition of RNAP2 from initiation to elongation. Signatures of the latter can be found genome-wide using chromatin immunoprecipitation followed by sequencing. We argue that this regulation leads to a robust and potentially tunable transcriptional response.
机译：组蛋白的转录后修饰在基因调控中起重要作用,但这些标记是否是转录或在下游所造成后果的活跃调控因子仍不清楚。在这项研究中,Tim Stasevich等人利用荧光显微镜方法以高时间分辨率对单个活细胞中组蛋白乙酰化与“RNA聚合酶Ⅱ”活性之间的动态互动进行了调查。组蛋白H3 Lys27在一个活跃基因位点上的乙酰化会增强对一个转录激活因子的吸引,加速“RNA聚合酶Ⅱ”从启动到伸长的转变。这些发现表明,组蛋白乙酰化对转录激发的两个不同步骤有一个因果效应。%In eukaryotic cells, post-translational histone modifications have an important role in gene regulation. Starting with early work on histone acetylation, a variety of residue-specific modifications have now been linked to RNA polymerase Ⅱ (RNAP2) activity, but it remains unclear if these markers are active regulators of transcription or just passive byproducts. This is because studies have traditionally relied on fixed cell populations, meaning temporal resolution is limited to minutes at best, and correlated factors may not actually be present in the same cell at the same time. Complementary approaches are therefore needed to probe the dynamic interplay of histone modifications and RNAP2 with higher temporal resolution in single living cells. Here we address this problem by developing a system to track residue-specific histone modifications and RNAP2 phosphorylation in living cells by fluorescence microscopy. This increases temporal resolution to the tens-of-seconds range. Our single-cell analysis reveals histone H3 lysine-27 acetylation at a gene locus can alter downstream transcription kinetics by as much as 50%, affecting two temporally separate events. First acetylation enhances the search kinetics of transcriptional activators, and later the acetylation accelerates the transition of RNAP2 from initiation to elongation. Signatures of the latter can be found genome-wide using chromatin immunoprecipitation followed by sequencing. We argue that this regulation leads to a robust and potentially tunable transcriptional response.

著录项

  • 来源
    《Nature》 |2014年第7530期|272-275a3|共5页
  • 作者

    Timothy J. Stasevich; Yoko Hayashi-Takanaka; Yuko Sato; Kazumitsu Maehara; Yasuyuki Ohkawa; Kumiko Sakata-Sogawa; Makio Tokunaga; Takahiro Nagase; Naohito Nozaki; James G. McNally; Hiroshi Kimura;

  • 作者单位

    Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan,Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870, USA,Transcription Imaging Consortium, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA;

    Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan,Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Saitama, 332-0012, Japan,Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan;

    Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan,Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan;

    Department of Advanced Medical Initiatives, Faculty of Medicine, Kyushu University, Fukuoka, 812-8582, Japan;

    Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Saitama, 332-0012, Japan,Department of Advanced Medical Initiatives, Faculty of Medicine, Kyushu University, Fukuoka, 812-8582, Japan;

    Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan,RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, 230-0045, Japan;

    Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan,RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, 230-0045, Japan;

    Department of Biotechnology Research, Kazusa DNA Research Institute, Chiba, 292-0818, Japan;

    Mab Institute Inc., Sapporo, 001-0021, Japan;

    Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA,Institute for Soft Matter and Functional Materials, Helmholtz Zentrum Berlin, Berlin, 14109, Germany;

    Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan,Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Saitama, 332-0012, Japan,Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan;

  • 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