在XistRNA中的G-四重复折叠对抗PRC2活性,以逐步调节X染色体无活化
Yong Woo Lee1, Uri Weissbein1, Roy Blum1
1Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Molecular cell
|May 17, 2024
概括
在XistRNA中的RNAG四复合体 (rG4s) 调节了Polycomb抑制复合体2 (PRC2) 的活性. 折叠的rG4s抑制PRC2,控制不活跃的X染色体上的基因沉默.
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:
- 由于RNA对Polycomb抑制复合体2 (PRC2) 的调节还不太清楚.
- PRC2可以结合RNA G-四复合体 (rG4s),但它们在体内折叠和结合的偏好是未知的.
研究的目的:
- 调查xistRNA中折叠rG4s在调节PRC2活动和基因沉默中的作用.
- 为了确定PRC2是否优先结合折叠或展开的rG4s.
主要方法:
- 在小鼠胚胎干细胞中利用X无活化模型.
- 在XistRNA中识别了折叠的rG4s.
- 评估了对折叠和展开的rG4s的PRC2结合亲和力.
- 测量了PRC2基因组甲基转移酶活性和H3K27me3丰富度.
- 改性rG4s,以评估它们对PRC2招募,释放和催化活性的影响.
主要成果:
- 在XistRNA中发现了多个折叠的rG4s.
- PRC2优先结合折叠的rG4s.
- 高亲和度的rG4结合抑制了PRC2的基因组甲基转移酶活性.
- 稳定rG4s对不起H3K27me3在不活跃的X染色体上的丰富.
- 突变rG4s没有影响PRC2的招募,但促进了它的释放和激活,导致错位的H3K27me3标记和受损的基因沉默.
- 克西斯-PRC2复合体被困在S1区内,防止转移到S2.
结论:
- 基因组RNA G-四重复折叠是PRC2活动的关键调节者.
- rG4折叠控制了H3K27me3的丰富,并在不活跃的X染色体上逐步抑制基因沉默.
- 这种机制通过调节PRC2的局部化和活性来确保适当的染色体范围的基因沉默.
关键词:
在G-四重复合体中.G4 G4 G4 G4 的意思是什么?在 PRC2 中,PRC2 是 PRC2 的第一个类型.多镇压复合体 2 2结构 RNA 结构 RNA 结构在X无活化过程中,一个Xistist.没有编码的RNA.更多相关视频
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