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Mouse ZFP57 zinc fingers in complex with methylated DNAMouse ZFP57 zinc fingers in complex with methylated DNA
Structural highlights
Function[ZFP57_MOUSE] Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions. Required for the establishment of maternal methylation imprints at SNRPN locus. Acts as a transcriptional repressor in Schwann cells. Binds to a 5'-TGCCGC-3' consensus sequence and recognizes the methylated CpG within this element.[1] [2] [3] Publication Abstract from PubMedZinc 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 A 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. An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence.,Liu Y, Toh H, Sasaki H, Zhang X, Cheng X Genes Dev. 2012 Nov 1;26(21):2374-9. doi: 10.1101/gad.202200.112. Epub 2012 Oct, 11. PMID:23059534[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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