Structural basis for Klf4 recognition of methylated DNA

• Type of Material: Article
• Authors: Yiwei Liu, Emory University; Yusuf Olatunde Olanrewaju, Emory University; Yu Zheng, New England Biolabs; Hideharu Hashimoto, Emory University; Robert M. Blumenthal, The University of Toledo College of Medicine and Life Sciences; Xing Zhang, Emory University; Xiaodong Cheng, Emory University
• Language: English
• Date: 2014-04
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2014. Published by Oxford University Press.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://nar.oxfordjournals.org/content/42/8/4859
• Title of Journal or Parent Work: Nucleic Acids Research
• ISSN: 0305-1048
• Volume: 42
• Issue: 8
• Start Page: 4859
• End Page: 4867
• Grant/Funding Information: National Institutes of Health (NIH) [GM049245-20 to X.C.]; Funding for open access charge: Waived by Oxford University Press.; The Emory University School of Medicine supported the use of Southeast Regional Collaborative Access Team (SER-CAT) 22-BM beamline at the Advanced Photon Source, Argonne National Laboratory.; Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science; Georgia Research Alliance Eminent Scholar (to X.C.)
• Research Categories: Chemistry, Biochemistry; Health Sciences, General; Health Sciences, Immunology

Abstract

Transcription factor Krüppel-like factor 4 (Klf4), one of the factors directing cellular reprogramming, recognizes the CpG dinucleotide (whether methylated or unmodified) within a specific G/C-rich sequence. The binding affinity of the mouse Klf4 DNA-binding domain for methylated DNA is only slightly stronger than that for an unmodified oligonucleotide. The structure of the C-terminal three Krüppel-like zinc fingers (ZnFs) of mouse Klf4, in complex with fully methylated DNA, was determined at 1.85 Å resolution. An arginine and a glutamate interact with the methyl group. By comparison with two other recently characterized structures of ZnF protein complexes with methylated DNA, we propose a common principle of recognition of methylated CpG by C2H2 ZnF proteins, which involves a spatially conserved Arg–Glu pair.