一个平衡的染色体平台为TGF-β访问主调节器
Qiaoran Xi1, Zhanxin Wang, Alexia-Ileana Zaromytidou
1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Cell
|December 27, 2011
概括
节点信号激活胚胎干细胞分化,通过准平衡的基因素标记H3K9me3.3. 这种相互作用招募关键蛋白质,使细胞命运决定的主调节者的激活成为可能.
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.
- 干细胞生物学 干细胞生物学
- 分子信号传输的方法
背景情况:
- 不同化的主调节器被特定的染色体标记所沉默,保持激活的准备.
- 细胞外信号,如节点TGF-β,可以触发从平静状态到活跃状态的过渡.
研究的目的:
- 阐明节点TGF-β信号触发哺乳动物胚胎干细胞分化的机制.
- 为了研究特定的组织蛋白标记和蛋白质复合体在激活分化调节者的作用.
主要方法:
- 使用晶体结构分析蛋白质-DNA相互作用.
- 研究了TRIM33-Smad2/3复合物的结合与组织素的作用.
- 研究了HP1γ的位移和Pol II的招募.
主要成果:
- 节点信号利用平衡的组素标记H3K9me3来启动干细胞分化.
- TRIM33 PHD-Bromo 磁带与 H3K9me3 和 H3K18ac 结合,从而更容易获得差异化调节器.
- 这种相互作用取代HP1γ,允许Smad4-Smad2/3的招募和Pol II的激活,而Smad4增强了H3K18的乙化.
结论:
- 节点信号利用H3K9me3作为一个平台来激活干细胞分化的定位主调节器.
- 基因组修饰和蛋白质复合体之间的相互作用对于在分化过程中染色质可访问性和基因激活的动态变化至关重要.
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