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通过人类UHRF1的SRA域识别半甲基化DNA的结构基础

George V Avvakumov¹, John R Walker, Sheng Xue

¹Structural Genomics Consortium, University of Toronto, 100 College Street, Toronto, Ontario M5G 1L5, Canada.

|September 6, 2008

概括

UHRF1蛋白在DNA中识别甲基化CpG位,这对于维持细胞分裂期间表观遗传信息至关重要. 这一发现揭示了哺乳动物表观遗传的一种新机制.

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.
分子生物学分子生物学
结构生物学结构生物学

背景情况:

表观遗传依赖于DNA甲基化模式的高可靠性复制.
UHRF1 (ICBP90/Np95) 是一种E3结合酶,对于维持DNA甲基化至关重要.
UHRF1优先结合半甲基化DNA,并与DNMT1相互作用.

研究的目的:

阐明UHRF1对半甲基化DNA的识别的结构机制.
了解UHRF1如何对表观遗传代码的复制作出贡献.

主要方法:

在UHRF1 SRA域的X射线晶体学 (apo和DNA结合).
对UHRF1 SRA-DNA复合物的结构分析.
突变发生的研究.

主要成果:

确定了UHRF1 SRA域的晶体结构,包括含有甲基化DNA的复合物.
揭示了一种新的DNA结合机制,其中5-甲基细胞素被翻转出来.
确定了专门的循环,读取CpG位点,并在补充链上区分甲基化.

结论:

UHRF1利用一种独特的结构机制来识别甲基化CpG位点.
这一认识对于UHRF1在DNMT1介导的DNA甲基化维护中的作用至关重要.
通过mCpG识别,UHRF1作为复制表观遗传代码的关键因素.

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