DNA methylation presents distinct binding sites for human transcription factors

Shaohui Hu, Jun Wan, Yijing Su, Qifeng Song, Yaxue Zeng, Ha Nam Nguyen, Jaehoon Shin, Eric Cox, Hee Sool Rho, Crystal Woodard, Shuli Xia, Shuang Liu, Huibin Lyu, Guo Li Ming, Herschel Wade, Hongjun Song, Jiang Qian, Heng Zhu

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere00726
Issue number2
StatePublished - Sep 3 2013

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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