对HATs和HDACs的全基因组映射揭示了活跃和不活跃基因的不同功能
Zhibin Wang1, Chongzhi Zang, Kairong Cui
1Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|August 25, 2009
概括
基因组乙转移酶 (HATs) 和脱乙酶 (HDACs) 结合活性基因,HDACs重置染色素. 启动的不活跃基因显示动态的HAT/HDAC结合,而静默的基因缺乏HDACs.
科学领域:
- 表观遗传学和基因调控
- 分子生物学分子生物学
- 染色体动力学 染色体动力学
背景情况:
- 基斯乙化是活跃转录的关键标记.
- 基因组乙转移酶 (HATs) 和脱乙酶 (HDACs) 反对调节基因组乙化.
- 以前的理解将HAT与活跃基因和HDAC与非活跃基因联系在一起.
研究的目的:
- 为了绘制HATs和HDACs在染色质上的全基因组结合.
- 阐明HATs和HDACs在基因调节中的作用.
- 了解HAT和HDAC的准机制.
主要方法:
- 对HATs和HDACs的全基因组染色体映射.
- 对RNA聚合酶II (Pol II) 酸化的分析.
- 研究像H3K4甲基化这样的基因组修饰.
主要成果:
- 无论是HAT还是HDAC都存在于具有乙化组织素的活性基因中.
- 酸化RNA Pol II对HAT和HDAC都针对活跃基因的转录区域.
- 大多数人类HDAC的功能是去除活性基因的乙化,重置染色质.
- 通过H3K4甲基化启动的非活性基因表现出动态的HAT/HDAC结合,毒害它们进行激活.
- 没有H3K4甲基化的静态基因显示没有HDAC结合.
结论:
- HATs和HDACs被酸化RNA Pol II.动态招募到活跃基因中.
- HDACs在重置活性基因染色质中起着至关重要的作用.
- 动态的HAT/HDAC活动在原始化的非活跃基因中平衡了基因抑制和未来的激活.
- HDACs不参与维持非原始基因的沉默状态.
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