Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells

被引：138

作者：

Meilinger, Daniela ^{[1
]}

Fellinger, Karin ^{[1
]}

Bultmann, Sebastian ^{[1
]}

Rothbauer, Ulrich ^{[1
]}

Bonapace, Ian Marc ^{[2
]}

Klinkert, Wolfgang E. F. ^{[3
]}

Spada, Fabio ^{[1
]}

Leonhardt, Heinrich ^{[1
]}

机构：

[1] Univ Munich, Dept Biol 2, Ctr Integrated Prot Sci Munich, D-82152 Planegg Martinsried, Germany

[2] Univ Insubria, Dept Struct & Funct Biol, I-21052 Busto Arsizio, VA, Italy

[3] Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany

来源：

EMBO REPORTS | 2009年 / 10卷 / 11期

关键词：

DNA methylation; histone modification; epigenetics; silencing; Uhrf1; HEMI-METHYLATED DNA; SRA DOMAIN; PROTEIN NP95; UHRF1; REPLICATION; G9A; RECOGNITION;

D O I：

10.1038/embor.2009.201

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1259 / 1264

页数：6

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