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Structural basis for Klf4 recognition of methylated DNA.

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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4005678 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Structural basis for Klf4 recognition of methylated DNA.

Liu Yiwei Y Olanrewaju Yusuf Olatunde YO Zheng Yu Y Hashimoto Hideharu H Blumenthal Robert M RM Zhang Xing X Cheng Xiaodong X

Nucleic acids research 20140211 8

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. ...[more]

PMID: 24520114

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