Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Biochem Soc Trans. 2013 Jun;41(3):727-40. doi: 10.1042/BST20130028.
Vertebrate DNA can be chemically modified by methylation of the 5 position of the cytosine base in the context of CpG dinucleotides. This modification creates a binding site for MBD (methyl-CpG-binding domain) proteins which target chromatin-modifying activities that are thought to contribute to transcriptional repression and maintain heterochromatic regions of the genome. In contrast with DNA methylation, which is found broadly across vertebrate genomes, non-methylated DNA is concentrated in regions known as CGIs (CpG islands). Recently, a family of proteins which encode a ZF-CxxC (zinc finger-CxxC) domain have been shown to specifically recognize non-methylated DNA and recruit chromatin-modifying activities to CGI elements. For example, CFP1 (CxxC finger protein 1), MLL (mixed lineage leukaemia protein), KDM (lysine demethylase) 2A and KDM2B regulate lysine methylation on histone tails, whereas TET (ten-eleven translocation) 1 and TET3 hydroxylate methylated cytosine bases. In the present review, we discuss the most recent advances in our understanding of how ZF-CxxC domain-containing proteins recognize non-methylated DNA and describe their role in chromatin modification at CGIs.
脊椎动物的 DNA 可以通过在 CpG 二核苷酸背景下胞嘧啶碱基的 5 位甲基化进行化学修饰。这种修饰为 MBD（甲基-CpG 结合域）蛋白创造了一个结合位点，这些蛋白靶向被认为有助于转录抑制和维持基因组异染色质区域的染色质修饰活性。与广泛存在于脊椎动物基因组中的 DNA 甲基化不同，非甲基化 DNA 集中在称为 CGIs（CpG 岛）的区域。最近，一类编码 ZF-CxxC（锌指-CxxC）结构域的蛋白质已被证明能够特异性识别非甲基化 DNA，并将染色质修饰活性募集到 CGI 元件上。例如，CFP1（CxxC 指蛋白 1）、MLL（混合谱系白血病蛋白）、KDM（赖氨酸去甲基酶）2A 和 KDM2B 调节组蛋白尾部上的赖氨酸甲基化，而 TET（十一个转位）1 和 TET3 羟基化甲基化的胞嘧啶碱基。在本综述中，我们讨论了对 ZF-CxxC 结构域蛋白识别非甲基化 DNA 的最新理解进展，并描述了它们在 CGIs 染色质修饰中的作用。
