Np95 interacts with de novo DNA methyltransferases,Dnmt3a and Dnmt3b,and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells |
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| Authors: | Sebastian Bultmann Ulrich Rothbauer Ian Marc Bonapace Wolfgang E F Klinkert Fabio Spada Heinrich Leonhardt |
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| Institution: | 1.Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilians University Munich, Großhaderner Street 2, 82152 Planegg-Martinsried, Germany;2.Department of Structural and Functional Biology, University of Insubria, Via da Giussano 12, 21052 Busto Arsizio (VA), Italy;3.Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany |
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| Abstract: | Recent studies have indicated that nuclear protein of 95 kDa (Np95) is essential for maintaining genomic methylation by recruiting DNA methyltransferase (Dnmt) 1 to hemi‐methylated sites. Here, we show that Np95 interacts more strongly with regulatory domains of the de novo methyltransferases Dnmt3a and Dnmt3b. To investigate possible functions, we developed an epigenetic silencing assay using fluorescent reporters in embryonic stem cells (ESCs). Interestingly, silencing of the cytomegalovirus promoter in ESCs preceded DNA methylation and was strictly dependent on the presence of either Np95, histone H3 methyltransferase G9a or Dnmt3a and Dnmt3b. Our results indicate a regulatory role for Np95, Dnmt3a and Dnmt3b in mediating epigenetic silencing through histone modification followed by DNA methylation. |
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| Keywords: | DNA methylation histone modification epigenetics silencing Uhrf1 |
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