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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP
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Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP

机译：p300 / CBP在进化上保守并介导了所有赖氨酸4三甲基化组蛋白H3的动态乙酰化

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摘要

Histone modifications are reported to show different behaviors, associations, and functions in different genomic niches and organisms. We show here that rapid, continuous turnover of acetylation specifically targeted to all K4-trimethylated H3 tails (H3K4me3), but not to bulk histone H3 or H3 carrying other methylated lysines, is a common uniform characteristic of chromatin biology in higher eukaryotes, being precisely conserved in human, mouse, and Dro-sophila. Furthermore, dynamic acetylation targeted to H3K4me3 is mediated by the same lysine acetyltransferase, p300/cAMP response element binding (CREB)-binding protein (CBP), in both mouse and fly cells. RNA interference or chemical inhibition of p300/CBP using a newly discovered small molecule inhibitor, C646, blocks dynamic acetylation of H3K4me3 globally in mouse and fly cells, and locally across the promoter and start-site of inducible genes in the mouse, thereby disrupting RNA polymerase II association and the activation of these genes. Thus, rapid dynamic acetylation of all H3K4me3 mediated by p300/CBP is a general, evolutionarily conserved phenomenon playing an essential role in the induction of immediate-early (IE) genes. These studies indicate a more global function of p300/CBP in mediating rapid turnover of acetylation of all H3K4me3 across the nuclei of higher eukaryotes, rather than a tight promoter-restricted function targeted by complex formation with specific transcription factors.
机译：据报道，组蛋白修饰在不同的基因组生态位和生物中显示出不同的行为，关联和功能。我们在这里表明，快速，连续的乙酰化快速转换专门针对所有K4-三甲基化的H3尾巴（H3K4me3），而不是大量携带其他甲基化的赖氨酸的组蛋白H3或H3，是高级真核生物中染色质生物学的共同特征。在人类，小鼠和果蝇中都是保守的。此外，在小鼠和飞行细胞中，靶向H3K4me3的动态乙酰化都由相同的赖氨酸乙酰基转移酶，p300 / cAMP反应元件结合（CREB）结合蛋白（CBP）介导。使用新发现的小分子抑制剂C646的RNA干扰或对p300 / CBP的化学抑制可在小鼠和飞行细胞中全局阻断H3K4me3的动态乙酰化作用，并局部阻断小鼠中可诱导基因的启动子和起始位点，从而破坏RNA聚合酶II关联和这些基因的激活。因此，由p300 / CBP介导的所有H3K4me3的快速动态乙酰化是一种普遍的，进化上保守的现象，在诱导即早（IE）基因中起着至关重要的作用。这些研究表明，p300 / CBP在介导所有H3K4me3穿过高级真核生物核的乙酰化快速转换方面具有更全面的功能，而不是由具有特定转录因子的复合物形成所靶向的严格的启动子限制性功能。

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    Nicholas T. Crump; Catherine A. Hazzalin; Erin M. Bowers; Rhoda M. Alani; Philip A. Cole; Louis C. Mahadevan;

  • 作者单位

    Nuclear Signalling Laboratory, Department of Biochemistry, Oxford University, Oxford OX1 3QU, United Kingdom;

    Nuclear Signalling Laboratory, Department of Biochemistry, Oxford University, Oxford OX1 3QU, United Kingdom;

    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Nuclear Signalling Laboratory, Department of Biochemistry, Oxford University, Oxford OX1 3QU, United Kingdom;

  • 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 acetylation turnover; trichostatin a; p300/cbp inhibitor;

    机译：组蛋白乙酰化转换;曲古霉素a;p300 / cbp抑制剂;

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