DNA methylation presents distinct binding sites for human transcription factors
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/00726 |
| _version_ | 1811181465713508352 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shaohui Hu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:18:12Z |
| format | Article |
| id | doaj.art-8642ae0b23ca4623ab1a7419c8ee84c6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:12Z |
| publishDate | 2013-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8642ae0b23ca4623ab1a7419c8ee84c62022-12-22T04:32:17ZengeLife Sciences Publications LtdeLife2050-084X2013-09-01210.7554/eLife.00726DNA methylation presents distinct binding sites for human transcription factorsShaohui Hu0Jun Wan1Yijing Su2Qifeng Song3Yaxue Zeng4Ha Nam Nguyen5Jaehoon Shin6Eric Cox7Hee Sool Rho8Crystal Woodard9Shuli Xia10Shuang Liu11Huibin Lyu12Guo-Li Ming13Herschel Wade14Hongjun Song15Jiang Qian16Heng Zhu17Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesThe Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United StatesInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United StatesInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, United StatesInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; Hugo W Moser Research Institute at Kennedy Krieger, Johns Hopkins University School of Medicine, Baltimore, United StatesInstitute of Physics, Chinese Academy of Sciences, Beijing, ChinaInstitute of Physics, Chinese Academy of Sciences, Beijing, ChinaInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, United States; The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United StatesInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, United States; The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United StatesThe Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesDNA 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.https://elifesciences.org/articles/00726DNA methylationprotein-DNA interactionprotein microarraytranscription factorepigenetictranscription regulation |
| spellingShingle | 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 DNA methylation presents distinct binding sites for human transcription factors eLife DNA methylation protein-DNA interaction protein microarray transcription factor epigenetic transcription regulation |
| title | DNA methylation presents distinct binding sites for human transcription factors |
| title_full | DNA methylation presents distinct binding sites for human transcription factors |
| title_fullStr | DNA methylation presents distinct binding sites for human transcription factors |
| title_full_unstemmed | DNA methylation presents distinct binding sites for human transcription factors |
| title_short | DNA methylation presents distinct binding sites for human transcription factors |
| title_sort | dna methylation presents distinct binding sites for human transcription factors |
| topic | DNA methylation protein-DNA interaction protein microarray transcription factor epigenetic transcription regulation |
| url | https://elifesciences.org/articles/00726 |
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