DNA methylation presents distinct binding sites for human transcription factors

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:

دوره 2  شماره 

صفحات  -

تاریخ انتشار 2013