Structural basis for Klf4 recognition of methylated DNA

By Yiwei Liu, Y. Olanrewaju, Yu Zheng, H. Hashimoto, R. Blumenthal, Xing Zhang, Xiaodong Cheng. 2014

93 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

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In Molecular Biology

1. Dirk Schübeler
2. Jussi Taipale
3. Paul Adrian Ginno
4. P. Beachy
5. Benjamin L. Ebert
6. Siddhartha Jaiswal

Citations in the corpus

• Impact of cytosine methylation on DNA binding specificities of human transcription factors (2017, methodology): “This class included TFs that have previously been reported to weakly prefer mCpG, such as CEBPB (40), KLFs (19, 20, 41), and RFX5 (20) (fig.”
• Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence (2014, unknown): “Similar interactions occur with Klf4 (Liu et al. 2014), except that the 3 9 Gua is contacted by R at (cid:1) 7 rather than (cid:1) 8 (Supplemental Fig.”