高度丰富的BEND3可以防止在分化过程中过早激活双价基因
Jing Zhang1, Yan Zhang1, Qinglong You1,2
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Science (New York, N.Y.)
|February 10, 2022
概括
BEND3是一种CpG岛结合蛋白,对胚胎发育至关重要. 它通过稳定多抑制复合体2来防止双价基因的过早激活,确保适当的分化.
科学领域:
- 表观遗传学和发育生物学
- 分子和细胞生物学
背景情况:
- 由活性的和抑制性的基因修饰标记的双对应基因已准备好进行发育激活.
- 在发育过程中,CpG岛 (CGI) 甲基化在调节基因表达方面发挥着关键作用.
- 在调节基因表达和发育方面,BEND3蛋白的功能在很大程度上是未知的.
研究的目的:
- 研究BEND3在胚胎发育和基因调节中的作用.
- 阐明BEND3与DNA结合并影响基因表达的分子机制.
- 了解BEND3与多抑制复合物2 (PRC2) 等表观基因修饰物的相互作用.
主要方法:
- 用目标DNA对BEND3进行共结晶以确定其结构.
- 产生和分析BEND3剥离的小鼠胚胎和胚胎干细胞 (ESC).
- 染色体免疫沉 (ChIP) 测试用于评估双价基因的BEND3和PRC2占用率.
主要成果:
- BEND3是一种对DNA甲基化敏感的蛋白质,它与调节元素的CpG岛屿结合.
- 在胃前期,BEND3的丧失导致胚胎死亡.
- 3无ESC显示严重的分化缺陷与许多双价基因的过早激活.
- BEND3对于稳定地将PRC2引入到BEND3占用的双价基因至关重要,保持H3K27me3水平.
结论:
- BEND3作为一个关键的表观遗传调节剂,维持ESC中双价基因的沉默状态.
- 在早期发育过程中,BEND3的功能对于防止异常基因激活至关重要.
- 对BEND3的结构和功能洞察力强调了它在维护发展进步中的作用.
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