• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >TRIM24 links a non-canonical histone signature to breast cancer
【24h】

TRIM24 links a non-canonical histone signature to breast cancer

机译：TRIM24将非规范的组蛋白特征与乳腺癌联系起来

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

Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4meO) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.%组蛋白的翻译后修饰是基因表达调控中的一个关键机制.修饰发生在必需被组蛋白"阅读器"蛋白如实翻译的组合中.对转录和染色质调控因子TRlM24的晶体结构所做的一项研究表明,它是一种独特的组蛋白"阅读器",能够对组蛋白H3上的双标记进行组合识别.TRIM24涉及依赖于雌激素的基因的激发,在乳腺癌中异常表达.这项工作确定了染色体"阅读器"可能影响致癌作用的一个新路径.
机译：通过“阅读器”蛋白内独特的结构域识别修饰的组蛋白在基因表达的调节中起关键作用。同时识别具有多个标记的组蛋白的读者可以将复杂的染色质修饰模式转导为特定的生物学结果。在这里我们报告染色质调节剂三方基序包含24（TRIM24）在人类中通过串联植物同源域（PHD）和溴域（Bromo）区域作为双重组蛋白标记的阅读器。 TRIM24的PHD-Bromo区域的三维结构揭示了一个单一的功能单元，用于组合识别未修饰的H3K4（即，赖氨酸4，H3K4meO未修饰的组蛋白H3）和乙酰化的H3K23（组氨酸H3在赖氨酸23，H3K23ac处乙酰化）在同一组蛋白尾巴内。 TRIM24结合染色质和雌激素受体激活与细胞增殖和肿瘤发展相关的雌激素依赖性基因。 TRIM24的异常表达与乳腺癌患者的生存负相关。 TRIM24的PHD-Bromo通过非规范的组蛋白签名为染色质激活提供了结构原理，从而建立了染色质阅读器可能影响癌症发病机理的新途径。 。修饰发生在必需被组蛋白“阅读器”蛋白如实译的组合中。对转录和染色质转化因子TRlM24的晶体结构进行的一项研究表明，它是一种独特的组蛋白“阅读器” ，能够对组蛋白H3的双标记进行组合识别.TRIM24涉及依赖于雌激素的基因的激发，在糖尿病中异常表达。其中工作确定了染色体“阅读器”可能影响致癌作用的一个新路径。

著录项

  • 来源
    《Nature》 |2010年第7326期|p.927-932ⅲ|共7页
  • 作者

    Wen-Wei Tsai; Zhanxin Wang; Teresa T. Yiu; Kadir C. Akdemir; Weiya Xia; Stefan Winter; Cheng-Yu Tsai; Xiaobing Shi; Dirk Schwarzer; William Plunkett; Bruce Aronow; Or Gozani; Wolfgang Fischle; Mien Chie Hung; Dinshaw J. Patel; Michelle Craig Barton;

  • 作者单位

    Department of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnStructurai Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;

    rnDepartment of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA,Centers for Cancer Epigenetics and Stem Cell and Developmental Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnCenters for Cancer Epigenetics and Stem Cell and Developmental Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA,Department of Biostatistics and Bioinformatics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, University of Texas M.D.Anderson Cancer Center. Houston, Texas 77030, USA;

    rnLaboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11,37077 Goettingen, Germany;

    rnDepartment of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnDepartment of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA,Centers for Cancer Epigenetics and Stem Cell and Developmental Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnDepartment of Chemical Biology/Protein Chemistry, Leibniz-lnstitutfur Molekulare Pharmakologie (FMP), Robert-Roessle-Strasse 10, 13125 Berlin, Germany;

    rnDepartment of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnComputational Medicine Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;

    rnDepartment of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnLaboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11,37077 Goettingen, Germany;

    rnDepartment of Molecular and Cellular Oncology, University of Texas M.D.Anderson Cancer Center. Houston, Texas 77030, USA,Department of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;

    rnStructurai Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;

    rnDepartment of Biochemistry and Molecular Biology, Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA,Centers for Cancer Epigenetics and Stem Cell and Developmental Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, 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