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基因组RNA结合选择自体基因,并依赖重复B来调节它们的表达

Shengze Yao^1,2, Yesu Jeon^1,2, Barry Kesner^1,2

¹Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

bioRxiv : the preprint server for biology

|August 2, 2024

概括

作为X染色体失活的关键,XistRNA针对大约100个小鼠自身基因. 重复B对于这种中转功能至关重要,其向可以被小分子抑制剂破坏.

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.
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

Xist是一种长非编码RNA,对X染色体无活化 (XCI) 是必不可少的.
传统上,Xist被认为是cis作用的RNA,只与不活跃的X染色体 (Xi) 结合.
有证据表明,Xist可能具有超越Xi的功能.

研究的目的:

为了调查XistRNA是否针对不活跃X染色体以外的基因.
为了确定这些非目标基因的特征和功能.
确定Xist的重复B动机及其潜在的小分子抑制剂在其中转活性中的作用.

主要方法:

使用雌性小鼠胚胎干细胞 (ES) 和小鼠胚胎纤维细胞 (MEF) 作为模型.
使用分子技术分析了XistRNA局部化和结合模式.
研究了Xist过度表达,重复B删除和Xist抑制剂 (X1) 治疗对基因表达的影响.

主要成果:

发现XistRNA在ES和MEF细胞中局部化并与大约100个自体基因结合.
目标基因具有活跃的染色质状态,并且位于Polycomb-poor区域,与人类的XIST模式不同.
结向下调节自体基因表达而不会导致完全沉默,这种效应依赖于重复B并对X1抑制敏感.

结论:

基因组RNA在小鼠中表现出特定的自体基因的内转基因向.
重复B动机对于Xist的自体基因向和调节功能至关重要.
通过小分子抑制剂可以调节Xist的自体基因调节,提供潜在的治疗途径.

关键词:

重复 B,重复 B 的过程.一个X染色体不活化.这就是XistRNA.表观遗传调节表观遗传调节没有编码的RNA.跨作用作用的交互作用

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