On how mammalian transcription factors recognize methylated DNA.
On how mammalian transcription factors recognize methylated DNA.
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DOI：
10.4161/epi.23632
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发表时间：
2013-02
期刊：
影响因子：
3.7
通讯作者：
Defossez PA
中科院分区：
文献类型：
--
作者：
Buck-Koehntop BA;Defossez PA
DNA甲基化是一种表观遗传标记，对哺乳动物的发育至关重要;它在从癌症到精神疾病的疾病中经常发生改变。DNA甲基化的存在吸引了专门的甲基DNA结合因子，然后可以招募染色质修饰剂。甲基化CpG结合蛋白（methyl-CpG binding proteins，MBPs）具有重要的生物学功能，可分为甲基化CpG结合结构域（methyl-CpG binding domain，MBD）、锌指结构域（zinc finger）和SET和RING指相关结构域（SET and RING finger-associated，SRA）三个结构家族。结合到甲基化DNA的MBD和SRA蛋白的结构先前已经确定，并显示出两种非常不同的甲基化DNA识别模式。最近，两种不同的锌指蛋白Kaiso和ZFP 57与甲基化DNA复合物的结构解析揭示了这个难题的最后一块。这些结构表明，两个甲基CpG结合锌指蛋白采用不同的甲基CpG结合模式。尽管如此，与MBD蛋白存在相似性，表明在各种MBP结构域中甲基-CpG识别的一些共性。这些新的见解对基因组中存在的许多其他锌指蛋白的分析以及甲基-CpG结合锌指蛋白的生物学具有重要意义。
DNA methylation is an epigenetic mark that is essential for the development of mammals; it is frequently altered in diseases ranging from cancer to psychiatric disorders. The presence of DNA methylation attracts specialized methyl-DNA binding factors that can then recruit chromatin modifiers. These methyl-CpG binding proteins (MBPs) have key biological roles and can be classified into three structural families: methyl-CpG binding domain (MBD), zinc finger, and SET and RING finger-associated (SRA) domain. The structures of MBD and SRA proteins bound to methylated DNA have been previously determined and shown to exhibit two very different modes of methylated DNA recognition. The last piece of the puzzle has been recently revealed by the structural resolution of two different zinc finger proteins, Kaiso and ZFP57, in complex with methylated DNA. These structures show that the two methyl-CpG binding zinc finger proteins adopt differential methyl-CpG binding modes. Nonetheless, there are similarities with the MBD proteins suggesting some commonalities in methyl-CpG recognition across the various MBP domains. These fresh insights have consequences for the analysis of the many other zinc finger proteins present in the genome, and for the biology of methyl-CpG binding zinc finger proteins.
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