A Common Mode of Recognition for Methylated CpG

• Authors: Yiwei Liu, Emory University; Xing Zhang, Emory University; Robert M. Blumenthal, The University of Toledo; Xiaodong Cheng, Emory University
• Journal Title: Trends in Biochemical Sciences
• Volume: Volume 38, Number 4
• Publisher: Elsevier (Cell Press) | 2013-04, Pages 177-183
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.tibs.2012.12.005
• Subjects: 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.