贾里德2/朱蒙吉协调控制PRC2酶活性和多能细胞中的基因占用
Jamy C Peng1, Anton Valouev, Tomek Swigut
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|January 13, 2010
概括
Jarid2是胚胎干细胞中的一个新的多抑制复合体2 (PRC2) 子单元. 它精细调整了用于发育和细胞分化的基因调控.
科学领域:
- 表观遗传学和基因调控
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 聚抑制复合体2 (PRC2) 对于调节胚胎干细胞 (ES) 发育基因至关重要.
- 了解PRC2在ES细胞和早期发育中的确切作用对于控制细胞命运至关重要.
- 已知Jarid2是一种Jumonji C (JmjC) 域蛋白,在多能细胞中被丰富.
研究的目的:
- 研究Jarid2作为ES细胞中PRC2的一个子单元的作用.
- 阐明Jarid2如何影响PRC2的基因组结合和酶活性.
- 确定Jarid2在早期发育过程中与PRC2相互作用的功能后果.
主要方法:
- 在ES细胞中对Jarid2,Ezh2和Suz12进行全基因组ChIP-seq分析.
- 生物化学试验,以评估PRC2基因组甲基转移酶活性.
- 使用Xenopus laevis胚胎与Jarid2 knockdown进行的功能研究.
主要成果:
- 在ES细胞中,Jarid2被确定为PRC2的子单元.
- Jarid2和PRC2在相同的基因组区域共同定位.
- Jarid2增强了PRC2对向基因的招募,但抑制了其甲基转移酶活性,作为分子静止剂.
- 在Xenopus胚胎中,Jarid2 knockdown会破坏胃化基因的诱导和分化.
结论:
- 贾里德2是PRC2的关键组成部分,在多能细胞中调节其功能.
- 这种相互作用对于发育基因的精确表观遗传调节至关重要.
- 这些发现揭示了在早期细胞酸盐转换过程中控制组织素甲基化的新机制.
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