Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells
Chen, Poshen B.
Rando, Oliver J.
Fazzio, Thomas G.
UMass Chan AffiliationsProgram in Molecular Medicine
Program in Gene Function and Expression
Program in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
Chromatin Assembly and Disassembly
Embryonic Stem Cells
Gene Knockdown Techniques
Mi-2 Nucleosome Remodeling and Deacetylase Complex
RNA Polymerase II
Biochemistry, Biophysics, and Structural Biology
Genetics and Genomics
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AbstractNumerous chromatin regulators are required for embryonic stem (ES) cell self-renewal and pluripotency, but few have been studied in detail. Here, we examine the roles of several chromatin regulators whose loss affects the pluripotent state of ES cells. We find that Mbd3 and Brg1 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy. Furthermore, both Mbd3 and Brg1 play key roles in the biology of 5-hydroxymethylcytosine (5hmC): Mbd3 colocalizes with Tet1 and 5hmC in vivo, Mbd3 knockdown preferentially affects expression of 5hmC-marked genes, Mbd3 localization is Tet1-dependent, and Mbd3 preferentially binds to 5hmC relative to 5-methylcytosine in vitro. Finally, both Mbd3 and Brg1 are themselves required for normal levels of 5hmC in vivo. Together, our results identify an effector for 5hmC, and reveal that control of gene expression by antagonistic chromatin regulators is a surprisingly common regulatory strategy in ES cells.
SourceCell. 2011 Dec 23;147(7):1498-510. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43971
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