激素H3.3酸化可以放大刺激诱导的转录
Anja Armache1,2, Shuang Yang3, Alexia Martínez de Paz1
1Laboratory of Epigenetics and Immunity, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Nature
|July 24, 2020
概括
在Ser31中基因变异H3.3酸化 (H3.3S31ph) 能够在巨细胞中快速诱导基因. 这种标记会招募转录因子并排出抑制剂,从而促进更快的基因激活.
科学领域:
- 分子生物学
- 表观遗传学
- 细胞生物学
背景情况:
- 复杂生物中的基因诱导依赖于染色体调节.
- 在动态调节的染色质中丰富的基因组变异H3.3.
- 在诱导基因中实现快速,高水平转录的机制尚不清楚.
研究的目的:
- 研究基因突变H3.3在快速基因诱导中的作用.
- 识别促进转录的H3.3的特定特征.
- 阐明刺激反应基因调节的分子机制.
主要方法:
- 分析小鼠巨细胞中的基因组变化.
- 质谱测试以识别相互作用的蛋白质.
- 染色体免疫沉以评估基因组变异的局部化.
主要成果:
- 在快速诱导的基因中发生H3.3在Serine 31 (H3.3S31ph) 的酸化.
- H3.3S31ph可以选择性地激活组织甲基转移酶SETD2.
- H3.3S31ph促进了延伸核心压力器ZMYND11的弹射.
结论:
- H3.3S31ph是刺激反应基因的关键标记.
- 这种酸化为转录装置提供了优先访问权.
- 涉及H3.3酸化的专门机制调节了快速转录.
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