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Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells
Author(s) -
Meilinger Daniela,
Fellinger Karin,
Bultmann Sebastian,
Rothbauer Ulrich,
Bonapace Ian Marc,
Klinkert Wolfgang E F,
Spada Fabio,
Leonhardt Heinrich
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.201
Subject(s) - methyltransferase , epigenetics , dna methylation , biology , dnmt3b , histone methyltransferase , histone methylation , methylation , dna methyltransferase , histone , gene silencing , epigenomics , epigenetics of physical exercise , microbiology and biotechnology , genetics , dna , gene , gene expression
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.