DNA methylation presents distinct binding sites for human transcription factors
By Shaohui Hu, Jun Wan, Yijing Su, Qifeng Song, Yaxue Zeng, H. N. Nguyen, Jaehoon Shin, Eric Cox, Hee-Sool Rho, Crystal L. Woodard and 8 more. 2013
335 citations recorded by the source corpus.
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
Subfields: Molecular Biology
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In Molecular Biology
- Brian D. Strahl
- Dirk Schübeler
- Jussi Taipale
- Paul Adrian Ginno
- Scott B. Rothbart
- C. D. Allis
- Yi Zhang
- P. Beachy
Citations in the corpus
- Impact of cytosine methylation on DNA binding specificities of human transcription factors (2017, background): “This class included TFs that have previously been reported to weakly prefer mCpG, such as CEBPB (40), KLFs (19, 20, 41), and RFX5 (20) (fig.”
- Interpreting thelanguage of histone and DNA modifications (2014, background): “While a number of these proteins harbor DNA binding domains commonly found in transcription factors, including zinc fingers, homeoboxes, and helix–loop–helix domains [37,165], it is likely that many newly discovered DNA modification readers will engage their mark through novel motifs.”