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 language | English (US) |
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Pages (from-to) | 2374-2379 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 26 |
Issue number | 21 |
DOIs | |
State | Published - Nov 1 2012 |
Externally published | Yes |
Keywords
- CpG islands
- DNA methylation
- Epigenetics
- Imprinting
- TGCCGC element
- Zinc finger protein Zfp571
ASJC Scopus subject areas
- Genetics
- Developmental Biology