An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence
- 11 October 2012
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 26 (21), 2374-2379
- https://doi.org/10.1101/gad.202200.112
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.Keywords
This publication has 37 references indexed in Scilit:
- Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base ResolutionScience, 2012
- Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian GenomeCell, 2012
- Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation developmentCell Research, 2011
- The Role of MeCP2 in the BrainAnnual Review of Cell and Developmental Biology, 2011
- In Embryonic Stem Cells, ZFP57/KAP1 Recognize a Methylated Hexanucleotide to Affect Chromatin and DNA Methylation of Imprinting Control RegionsMolecular Cell, 2011
- Replication-Dependent Loss of 5-Hydroxymethylcytosine in Mouse Preimplantation EmbryosScience, 2011
- Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNAScience, 2011
- Solution structure and dynamic analysis of chicken MBD2 methyl binding domain bound to a target-methylated DNA sequenceNucleic Acids Research, 2011
- Diseases Associated with Genomic ImprintingProgress in Molecular Biology and Translational Science, 2011
- 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cellsGenome Biology, 2011