Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells

Ozlem Yildirim, Ruowang Li, Jui-Hung Hung, Poshen B. Chen, Xianjun Dong, Ly Sha Ee, Zhiping Weng, Oliver J. Rando*, Thomas G. Fazzio

*Corresponding author for this work

Research output: Contribution to journalArticle

311 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1498-1510
Number of pages13
JournalCell
Volume147
Issue number7
DOIs
StatePublished - 23 Dec 2011

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    Yildirim, O., Li, R., Hung, J-H., Chen, P. B., Dong, X., Ee, L. S., Weng, Z., Rando, O. J., & Fazzio, T. G. (2011). Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell, 147(7), 1498-1510. https://doi.org/10.1016/j.cell.2011.11.054