在人类早期发育过程中,XIST以SPEN-依赖的方式抑制X染色体活动
Charbel Alfeghaly1, Gaël Castel1, Emmanuel Cazottes1
1Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.
Nature structural & molecular biology
|June 4, 2024
概括
在X染色体失活 (XCI) 之前,XIST长非编码RNA (lncRNA) 会抑制基因表达. XIST XIST 这是一个很好的例子.
科学领域:
- 表观遗传学和基因调控
- 发展生物学 发展生物学
- 基因组学就是基因组学.
背景情况:
- 在胎盘哺乳动物中, lncRNA 启动 X 染色体无活化 (XCI).
- 在人类植入前胚胎中,XIST和XACT (X活性涂层转录) lncRNAs在X染色体上积聚而不会沉默.
- XACT可能对抗XIST功能,但其作用尚不清楚.
研究的目的:
- 研究XIST和XACT在原始人类胚胎干细胞中的功能.
- 阐明它们在早期发育期间塑造X染色体染色质和转录景观中的作用.
主要方法:
- 使用了天真的人类胚胎干细胞.
- 评估了XIST和XACT对X染色体染色体修饰和基因表达的影响.
- 研究了XIST函数的SPEN依赖机制.
主要成果:
- XIST触发压制性基因组修饰,并以SPEN-依赖的方式抑制X链接基因转录.
- XACT 缺乏症并没有显著改变 XIST 活性或 X 相关基因表达.
- 在XCI完成之前,XIST是功能性的,这表明一个暂时的剂量补偿过程.
结论:
- 在完全启动XCI之前,XIST积极抑制基因表达.
- 在这种情况下,XACT似乎不会对抗XIST函数.
- XCI和基因抑制具有共同的监管因素.
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