期刊
ELIFE
卷 2, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.00726
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资金
- National Institutes of Health [R01 GM076102, U54 RR020839, U24 CA160036, U54 HG006434, R21 EY021897, NS047344, MH087874, ES021957, NS048271, HD069184]
- The Simons Foundation Autism Research Initiative
- Dr Miriam and Sheldon G Adelson Medical Research Foundation
- Maryland Stem Cell Research Fund [2009-MSCRFE-0063-00, 2012-MSCRFII-0063-00]
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.
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