在Clr4 (Suv39h) 中自甲基化诱导的形状转换保持了表观遗传稳定性
Nahid Iglesias1,2, Mark A Currie1,2, Gloria Jih1,2
1Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Nature
|July 28, 2018
概括
研究人员发现H3K9甲基转移酶Clr4是如何内在抑制和自动激活的. 这种调节可以防止异常基因沉默,并保持表观遗传稳定性,这是人类保存的机制.
科学领域:
- 表观遗传学
- 分子生物学
- 基因调控
背景情况:
- 基因沉默和基因组稳定性至关重要.
- H3K9甲基转移酶通过正反循环建立和维持异色素.
- 限制H3K9甲基转移酶活动以防止异常沉默的机制尚未完全理解.
研究的目的:
- 研究H3K9甲基转移酶Clr4的自身抑制和自身激活机制.
- 了解Clr4的活性是如何调节的,以防止异常的异性染色体形成.
- 探索内在调节在维持表观遗传稳定的作用.
主要方法:
- 用于研究酶活性的生物化学测试.
- 进行X射线结晶学以确定酶结构.
- 位点定向的突变,以评估调节循环的功能.
主要成果:
- 由于内部循环阻断基质结合口袋,Clr4存在于自抑制的形状.
- 在循环中 lysines 的自甲基化触发了 conformational 开关,增强了 Clr4 的活性.
- 破坏这种调节的突变会导致异常的H3K9me,异性染色质的丧失和生长缺陷.
结论:
- 对于精确的H3K9甲基化,Cr4的内在抑制和自动激活至关重要.
- 这种调节机制可以防止表观遗传不稳定和异常基因沉默.
- 自抑制机制在其他H3K9甲基转移酶中保持,包括人类同类.
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