SPEN 集成了 X 失活的转录和表观遗传控制
François Dossin1, Inês Pinheiro2, Jan J Żylicz2,3
1European Molecular Biology Laboratory, Director's Unit, Heidelberg, Germany.
Nature
|February 7, 2020
概括
通过结合XistRNA和调用静音机制,SPEN蛋白对于启动X染色体失活 (XCI) 是至关重要的. 它的SPOC域是基因沉默的关键,将Xist与转录因子集成在一起.
科学领域:
- 表观遗传学
- RNA生物学
- 哺乳动物的发展
背景情况:
- 长非编码RNA (lncRNA) Xist是X染色体失活 (XCI) 的核心.
- 通过Xist调解基因沉默的机制尚未完全理解.
- SPEN (拼接调节蛋白ENsomtic) 已被确定为一个结合的蛋白质.
研究的目的:
- 调查SPEN在XCI中的体内作用.
- 阐明SPEN在XCI中的作用机制.
- 定义SPEN的功能域和蛋白质相互作用体.
主要方法:
- 在小鼠体内的研究,包括植入前胚胎和胚胎干细胞.
- 基因表达和染色体占用量的分析.
- 生物化学测试以确定蛋白质相互作用体和功能域.
主要成果:
- 在小鼠早期发育过程中,SPEN对于启动XCI至关重要.
- 在Xist上调时,SPEN被招募到X染色体中,并准活性基因调节元素.
- SPEN 的 SPOC 域足以抑制基因,并与关键的表观遗传调节剂相互作用.
结论:
- 在体内,SPEN作为XCI启动的关键协调者.
- SPEN将XistRNA与转录机制和表观遗传修饰剂进行集成.
- SPOC域是SPEN介导的基因沉默的一个关键效应因子.
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