An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence
- 1Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA;
- 2Division of Epigenomics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
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.
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Footnotes
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↵3 Corresponding author
E-mail xcheng{at}emory.edu
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.202200.112.
- Received July 25, 2012.
- Accepted September 10, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press