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

Yiwei Liu, Hidehiro Toh, Hiroyuki Sasaki, Xing Zhang, Xiaodong Cheng

    Research output: Contribution to journalArticle

    85 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)2374-2379
    Number of pages6
    JournalGenes and Development
    Volume26
    Issue number21
    DOIs
    Publication statusPublished - Nov 1 2012

    All Science Journal Classification (ASJC) codes

    • Genetics
    • Developmental Biology

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