A Common Mode of Recognition for Methylated CpG

• Type of Material: Article
• Authors: Yiwei Liu, Emory University; Xing Zhang, Emory University; Robert M. Blumenthal, The University of Toledo; Xiaodong Cheng, Emory University
• Language: English
• Date: 2013-04
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.tibs.2012.12.005
• Title of Journal or Parent Work: Trends in Biochemical Sciences
• ISSN: 0968-0004
• Volume: 38
• Issue: 4
• Start Page: 177
• End Page: 183
• Grant/Funding Information: X.C. is a Georgia Research Alliance Eminent Scholar; The U.S. National Institutes of Health (grant GM049245-19 to X.C. and X.Z.) and National Science Foundation (grant MCB-0964728 to R.M.B.) supported this work.
• Research Categories: Chemistry, Biochemistry

Abstract

Much is known about vertebrate DNA methylation, however it is not known how methylated CpG within particular sequences is recognized. Two recent structures of C2H2 zinc finger (ZnF) proteins, in complex with methylated DNA, reveal a common recognition mode for 5-methylcytosine (5mC) that involves a 5mC-Arg-G triad. In the two ZnF proteins, an arginine that precedes the first Zn-binding histidine (RH motif) can interact with 5mCpG or TpG dinucleotide. Among a family of >300 human KRAB (Krüppel-associated box) domain-containing ZnF proteins examined, two-thirds contain at least one ZnF that includes an RH motif. We propose that the RH-ZnF motifs provide specificity for 5mCpG, while the neighboring ZnF fingers recognize the surrounding DNA sequence context.