作为DNA甲基化的读取器和效应器的转录因子。
Transcription factors as readers and effectors of DNA methylation.
作者信息
Zhu Heng, Wang Guohua, Qian Jiang
机构信息
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Edward Miller Research Building, 733 North Broadway, Baltimore, Maryland 21205, USA.
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
出版信息
Nat Rev Genet. 2016 Aug 1;17(9):551-65. doi: 10.1038/nrg.2016.83.
Recent technological advances have made it possible to decode DNA methylomes at single-base-pair resolution under various physiological conditions. Many aberrant or differentially methylated sites have been discovered, but the mechanisms by which changes in DNA methylation lead to observed phenotypes, such as cancer, remain elusive. The classical view of methylation-mediated protein-DNA interactions is that only proteins with a methyl-CpG binding domain (MBD) can interact with methylated DNA. However, evidence is emerging to suggest that transcription factors lacking a MBD can also interact with methylated DNA. The identification of these proteins and the elucidation of their characteristics and the biological consequences of methylation-dependent transcription factor-DNA interactions are important stepping stones towards a mechanistic understanding of methylation-mediated biological processes, which have crucial implications for human development and disease.
最近的技术进步使得在各种生理条件下以单碱基对分辨率解码DNA甲基化组成为可能。已经发现了许多异常或差异甲基化位点，但DNA甲基化变化导致诸如癌症等观察到的表型的机制仍然难以捉摸。甲基化介导的蛋白质-DNA相互作用的传统观点是，只有具有甲基化CpG结合域（MBD）的蛋白质才能与甲基化DNA相互作用。然而，越来越多的证据表明，缺乏MBD的转录因子也能与甲基化DNA相互作用。鉴定这些蛋白质并阐明它们的特征以及甲基化依赖性转录因子-DNA相互作用的生物学后果，是朝着从机制上理解甲基化介导的生物学过程迈出的重要一步，而这对人类发育和疾病具有至关重要的意义。
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