DNA methylation presents distinct binding sites for human transcription factors
Open Access
- 3 September 2013
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
- Vol. 2, e00726
- https://doi.org/10.7554/elife.00726
Abstract
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.Keywords
Funding Information
- National Institutes of Health (R01 GM076102, U54 RR020839, U24 CA160036, U54 HG006434)
- National Institutes of Health (R21 EY021897)
- National Institutes of Health (NS047344, MH087874, ES021957)
- The Simons Foundation Autism Research Initiative
- National Institutes of Health (NS048271, HD069184)
- Dr Miriam and Sheldon G Adelson Medical Research Foundation
- Maryland Stem Cell Research Fund (2009-MSCRFE-0063-00, 2012-MSCRFII-0063-00)
- National Institutes of Health (R01 GM076102, U54 RR020839, U24 CA160036, U54 HG006434)
- National Institutes of Health (R21 EY021897)
- National Institutes of Health (NS047344, MH087874, ES021957)
- Simons Foundation
- National Institutes of Health (NS048271, HD069184)
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Maryland Stem Cell Research Fund (2009-MSCRFE-0063-00, 2012-MSCRFII-0063-00)
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