Article

A Novel Regulatory Factor Recruits the Nucleosome Remodeling Complex to Wingless Integrated (WNT) Signaling Gene Promoters in Mouse Embryonic Stem cells.

UCLA, United States.
Journal of Biological Chemistry (Impact Factor: 4.6). 10/2012; DOI: 10.1074/jbc.M112.416545
Source: PubMed

ABSTRACT Nucleosome Remodeling and Deacetylation (NuRD) complex is required for modulating the transcription of essential pluripotency genes in ESC self-renewal. MBD3 is considered a key player in the formation of a functional NuRD complex. The recruitment of MBD3 to methylated promoters may require other prerequisite factors. We show that Cyclin Dependent Kinase 2-Associated Protein 1 (CDK2AP1), an essential gene for early embryonic development, plays a role in pluripotency of ESC by engaging MBD3 to the promoter region of Wnt signalling genes. The occupancy of MBD3 on several promoters of Wnt genes was significantly lost in the absence of CDK2AP1, resulting in hyper-activation of Wnt. We propose that the transcriptional modulation of Wnt pathway mediated by NuRD requires the presence of essential auxiliary components, such as CDK2AP1, that may aid the association of the complex with the specific focal region of the target promoters.

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