• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >The expanding landscape of 'oncohistone' mutations in human cancers
【24h】

The expanding landscape of 'oncohistone' mutations in human cancers

机译：人类癌症中“ onhihistone”突变的景观正在扩大

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

Mutations in epigenetic pathways are common oncogenic drivers. Histones, the fundamental substrates for chromatin-modifying and remodelling enzymes, are mutated in tumours including gliomas, sarcomas, head and neck cancers, and carcinosarcomas. Classical 'oncohistone' mutations occur in the N-terminal tail of histone H3 and affect the function of polycomb repressor complexes 1 and 2 (PRC1 and PRC2). However, the prevalence and function of histone mutations in other tumour contexts is unknown. Here we show that somatic histone mutations occur in approximately 4% (at a conservative estimate) of diverse tumour types and in crucial regions of histone proteins. Mutations occur in all four core histones, in both the N-terminal tails and globular histone fold domains, and at or near residues that contain important post-translational modifications. Many globular domain mutations are homologous to yeast mutants that abrogate the need for SWI/SNF function, occur in the key regulatory 'acidic patch' of histones H2A and H2B, or are predicted to disrupt the H2B-H4 interface. The histone mutation dataset and the hypotheses presented here on the effect of the mutations on important chromatin functions should serve as a resource and starting point for the chromatin and cancer biology fields in exploring an expanding role of histone mutations in cancer.
机译：表观遗传途径的突变是常见的致癌驱动因素。组蛋白是染色质修饰和重塑酶的基本底物，在包括神经胶质瘤，肉瘤，头颈癌和癌肉瘤的肿瘤中发生突变。经典的“癌蛋白”突变发生在组蛋白H3的N末端尾部，并影响多梳阻遏物复合物1和2（PRC1和PRC2）的功能。然而，在其他肿瘤环境中，组蛋白突变的发生率和功能尚不清楚。在这里，我们显示体细胞组蛋白突变发生在大约4％（保守估计）的各种肿瘤类型和组蛋白的关键区域中。突变发生在所有四个核心组蛋白中，在N末端尾部和球状组蛋白折叠域中，以及在含有重要翻译后修饰的残基处或附近残基。许多球状结构域突变都与酵母突变体同源，后者消除了SWI / SNF功能的需要，发生在组蛋白H2A和H2B的关键调控“酸性区”中，或被认为会破坏H2B-H4界面。此处介绍的组蛋白突变数据集和有关突变对重要染色质功能影响的假设应作为染色质和癌症生物学领域探索组蛋白突变在癌症中不断扩大作用的资源和起点。

著录项

  • 来源
    《Nature》 |2019年第7749期|473-478|共6页
  • 作者

    Nacev Benjamin A.; Feng Lijuan; Bagert John D.; Lemiesz Agata E.; Gao JianJiong; Soshnev Alexey A.; Kundra Ritika; Schultz Nikolaus; Muir Tom W.; Allis C. David;

  • 作者单位

    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA|Rockefeller Univ, Lab Chromatin Biol & Epigenet, 1230 York Ave, New York, NY 10021 USA;

    Rockefeller Univ, Lab Chromatin Biol & Epigenet, 1230 York Ave, New York, NY 10021 USA;

    Princeton Univ, Dept Chem, Princeton, NJ 08544 USA;

    Rockefeller Univ, Lab Chromatin Biol & Epigenet, 1230 York Ave, New York, NY 10021 USA;

    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA;

    Rockefeller Univ, Lab Chromatin Biol & Epigenet, 1230 York Ave, New York, NY 10021 USA;

    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA;

    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA;

    Princeton Univ, Dept Chem, Princeton, NJ 08544 USA;

    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA|Rockefeller Univ, Lab Chromatin Biol & Epigenet, 1230 York Ave, New York, NY 10021 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