DNA methylation presents distinct binding sites for human transcription factors
Year: 2013
Type: article
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. DOI:http://dx.doi.org/10.7554/eLife.00726.001.
Source: eLife
DOI: 10.7554/elife.00726
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Simons Foundation, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Maryland Stem Cell Research Fund, Simons Foundation Autism Research Initiative, National Institutes of Health, National Institute of Mental Health, National Human Genome Research Institute, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: DNA-Binding Activity of Human Proteins, Impact of Bisphenol A on neural stem cells and development in the adult brain, G2828395219, Neurobiology of MeCP2 in adult neurogenesis, Biochemistry, Cellular and Molecular Biology Program, G3753613124, G5241774018, G5268478619, Proteome Characterization Center: A Genoproteomics Pipeline for Cancer Biomarkers, G5539111302, G6121259306, Monospecific monoclonal antibodies against human transcription factors, Networks, Pathways and Dynamics of Lysine Modification, Dynamic Usage of Network Motifs in Retinal Development and Diseases, G9000018768, G9000161916, G9000222528, G9000253556, G9000302091, G9000320123
OpenAlex ID: W2128059998