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对CBP的RNA结合刺激了基因素乙化和转录
Daniel A Bose1, Greg Donahue1, Danny Reinberg2
1Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell
|January 14, 2017
概括
CBP/ p300 蛋白直接与增强 RNA (eRNA) 结合. 这种相互作用刺激了它们的活性,影响了活性增强剂的基因表达和染色质结构.
科学领域:
- 分子生物学
- 表观遗传学
- 基因调控
背景情况:
- CBP/p300是基因表达调节的关键转录协活性剂.
- 增强剂是关键的 cis 调节元件,其特征是结合 CBP/ p300 和产生活性转录增强剂 RNA (eRNA).
- 活性增强剂表现出CBP/ p300依赖的基因素乙化,这是开放色素的标志.
研究的目的:
- 研究CBP/p300和RNA分子之间的直接相互作用.
- 确定RNA结合对CBP/p300活动的功能后果.
- 阐明ERNA-CBP/p300相互作用在增强剂功能和基因调节中的作用.
主要方法:
- 检测CBP/p300-RNA相互作用的体内和体外结合测定.
- 测量基因酸转移酶 (HAT) 来测量CBP/p300酶活性.
- 基因乙化标记 (例如,H3K27ac) 和基因表达变化的分析.
主要成果:
- CBP/p300蛋白直接与RNA分子结合,其中包括大量的eRNA.
- 在CBP/p300的HAT域内的RNA结合区域以RNA依赖的方式刺激其HAT活性.
- 与CBP/ p300的eRNA相互作用导致特定的基因素乙化变化,并调节活性增强剂的基因表达.
结论:
- eRNA与CBP/p300直接相互作用,调节它们的功能.
- 这种通过RNA介导的CBP/ p300活性对于在活性增强剂中建立染色质结构至关重要.
- CBP/ p300- eRNA相互作用在增强剂对基因表达的精确调节中起着关键作用.
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