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6797748 
Journal Article 
DNA methylation presents distinct binding sites for human transcription factors 
Hu, S; Wan, J; Su, Y; Song, Q; Zeng, Y; Nguyen, HN; Shin, J; Cox, E; Rho, HS; Woodard, C; Xia, S; Liu, S; Lyu, H; Ming, GL; Wade, H; Song, H; Qian, J; Zhu, H 
2013 
1 
eLife
ISSN: 2050-084X 
2 
e00726 
English 
24015356 
WOS:000328626200003 
DNA methylation, especially CpG methylation at promoter regions, has been generally considered as a potent epigenetic modification that prohibits transcription factor (TF) recruitment, resulting in transcription suppression. Here, we used a protein microarray-based approach to systematically survey the entire human TF family and found numerous purified TFs with methylated CpG (mCpG)-dependent DNA-binding activities. Interestingly, some TFs exhibit specific binding activity to methylated and unmethylated DNA motifs of distinct sequences. To elucidate the underlying mechanism, we focused on Kruppel-like factor 4 (KLF4), and decoupled its mCpG- and CpG-binding activities via site-directed mutagenesis. Furthermore, KLF4 binds specific methylated or unmethylated motifs in human embryonic stem cells in vivo. Our study suggests that mCpG-dependent TF binding activity is a widespread phenomenon and provides a new framework to understand the role and mechanism of TFs in epigenetic regulation of gene transcription. DOI:http://dx.doi.org/10.7554/eLife.00726.001.