Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells
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Authors
Yildirim, OzlemLi, Ruowang
Hung, Jui-Hung
Chen, Poshen B.
Dong, Xianjun
Ee, Ly-Sha
Weng, Zhiping
Rando, Oliver J.
Fazzio, Thomas G.
UMass Chan Affiliations
Program in Molecular MedicineProgram in Gene Function and Expression
Program in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2011-12-23Keywords
AnimalsChromatin Assembly and Disassembly
Cytosine
DNA Helicases
DNA-Binding Proteins
Embryonic Stem Cells
Gene Knockdown Techniques
Humans
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Mice
Nuclear Proteins
Proto-Oncogene Proteins
RNA Polymerase II
Transcription Factors
Biochemistry, Biophysics, and Structural Biology
Genetics and Genomics
Metadata
Show full item recordAbstract
Numerous 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.Source
Cell. 2011 Dec 23;147(7):1498-510. Link to article on publisher's siteDOI
10.1016/j.cell.2011.11.054Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43971PubMed ID
22196727Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2011.11.054