Xist lncRNA 与 SHARP 直接相互作用,通过 HDAC3 沉默转录
Colleen A McHugh1, Chun-Kan Chen1, Amy Chow1
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.
研究人员确定了与Xist长非编码RNA (lncRNA) 相互作用的蛋白质,以了解X染色体不活化. SHARP,SMRT和HDAC3对于Xist介导的基因沉默和Polycomb Repressive Complex 2的招募至关重要.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 长非编码RNAs (lncRNAs) 通过多种机制调节基因表达.
- 在雌性哺乳动物中,Xist lncRNA启动X染色体不活化,但其蛋白质相互作用因子在很大程度上仍未知.
- 目前的方法不足以全面识别与lncRNAs直接相互作用的蛋白质.
研究的目的:
- 开发一种用于净化 lncRNAs 和识别直接相互作用的蛋白质的方法.
- 阐明Xist的蛋白相互作用网络及其在转录沉默中的作用.
主要方法:
- 开发一种 lncRNA 净化技术.
- 量化质谱测量用于识别与Xist.相互作用的蛋白质.
- 功能性测试以确定已识别的蛋白质在Xist介导沉默中的作用.
主要成果:
- 鉴定出十种蛋白质与Xist.特别相关.
- 发现SHARP,SAF-A和LBR对于Xist介导的转录沉默至关重要.
- 需要SHARP,SMRT和HDAC3来排除RNA聚合酶II,并将Polycomb Repressive Complex 2招募到不活跃的X染色体上.
结论:
- 通过直接与SHARP相互作用,招募SMRT,并激活HDAC3.3,Xist使转录沉默.
- 通过HDAC3去乙化基因组对于排除RNA聚合酶II和确定X染色体不活化至关重要.
- 这些已识别的蛋白质为Xist功能的分子机制提供了关键的见解.
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