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An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence.

ABSTRACT: Zinc finger transcription factor Zfp57 recognizes the methylated CpG within the TGCCGC element. We determined the structure of the DNA-binding domain of Zfp57, consisting of two adjacent zinc fingers, in complex with fully methylated DNA at 1.0 Å resolution. The first zinc finger contacts the 5' half (TGC), and the second recognizes the 3' half (CGC) of the recognition sequence. Zfp57 recognizes the two 5-methylcytosines (5mCs) asymmetrically: One involves hydrophobic interactions with Arg178, which also interacts with the neighboring 3' guanine and forms a 5mC-Arg-G interaction, while the other involves a layer of ordered water molecules. Two point mutations in patients with transient neonatal diabetes abolish DNA-binding activity. Zfp57 has reduced binding affinity for unmodified DNA and the oxidative products of 5mC.

SUBMITTER: Liu Y

PROVIDER: S-EPMC3489995 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence.

Liu Yiwei Y Toh Hidehiro H Sasaki Hiroyuki H Zhang Xing X Cheng Xiaodong X

Genes & development 20121011 21

Zinc finger transcription factor Zfp57 recognizes the methylated CpG within the TGCCGC element. We determined the structure of the DNA-binding domain of Zfp57, consisting of two adjacent zinc fingers, in complex with fully methylated DNA at 1.0 Å resolution. The first zinc finger contacts the 5' half (TGC), and the second recognizes the 3' half (CGC) of the recognition sequence. Zfp57 recognizes the two 5-methylcytosines (5mCs) asymmetrically: One involves hydrophobic interactions with Arg178, w ...[more]

PMID: 23059534

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