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Publication : Cdk2ap1 is required for epigenetic silencing of Oct4 during murine embryonic stem cell differentiation.

First Author  Deshpande AM Year  2009
Journal  J Biol Chem Volume  284
Issue  10 Pages  6043-7
PubMed ID  19117947 Mgi Jnum  J:147894
Mgi Id  MGI:3842877 Doi  10.1074/jbc.C800158200
Citation  Deshpande AM, et al. (2009) Cdk2ap1 is required for epigenetic silencing of Oct4 during murine embryonic stem cell differentiation. J Biol Chem 284(10):6043-7
abstractText  Oct4 is a known master regulator of stem cell renewal and differentiation. Expression of Oct4 during differentiation is regulated by promoter methylation by the nucleosome remodeling and histone deacetylation (NuRD) complex. Here, we show that Cdk2ap1, a negative regulator of Cdk2 function and cell cycle, promotes Oct4 promoter methylation during murine embryonic stem cell differentiation to down-regulate Oct4 expression. We further show that this repressor function of Cdk2ap1 is dependent on its physical interaction with the methyl DNA-binding protein, Mbd3. Our data support a potential molecular link between the known differentiation promoters, including bone morphogenetic proteins and transforming growth factor signaling, and embryonic stem cell differentiation.
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