通过与LINE-1调节元件的结合,通过组织基因甲基转移酶EHMT2对与全能性相关的基因位点进行协调抑制
K Chatterjee1, C M Uyehara1, K Kasliwal1
1Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
bioRxiv : the preprint server for biology
|January 7, 2025
概括
作为一种染色素抑制剂的EHMT2,控制着小鼠干细胞转化为双细胞样细胞的过程. 它抑制特定的基因集群和内源性逆转录病毒元素,影响早期哺乳动物的发育.
科学领域:
- 发育生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 像老鼠胚胎干细胞 (mESCs) 一样,天真的多能干细胞可以分化为2细胞类细胞 (2CLCs).
- 这种过渡反映了在胚胎活化 (ZGA) 过程中的早期哺乳动物胚胎发育.
- 了解这个过程可以让我们了解植入前的开发过程.
研究的目的:
- 研究染色体抑制剂EHMT2在mESC-to-2CLC过渡中的作用.
- 定义EHMT2在2CLCs中调节基因表达的分子机制.
主要方法:
- 用于用于急性蛋白质枯竭和免疫沉的多用途等位基因.
- 分析了EHMT2目标基因及其染色体参与.
- 研究了EHMT2与LINE-1元素,DPPA2/4,ZFP462和增强剂的相互作用.
主要成果:
- 在2CLC中,EHMT2通过从LINE-1元素传播的H3K9me2直接抑制基因集群和内源逆转录病毒元素 (ERV).
- EHMT2可以抵消激活器DPPA2/4对ERV的招募.
- EHMT2的枯竭增强了ZGA相关的转录,并促进了mESC-to-2CLC的过渡.
- 通过ZFP462和非重复增强剂,EHMT2抑制了与生殖层相关的转录.
结论:
- EHMT2减弱了小鼠多能干细胞的分化潜力.
- 由EHMT2.2定义的特定位置的转录抑制机制.
- 通过控制2CLCs中的基因表达,EHMT2在调节早期哺乳动物发育方面发挥着关键作用.
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