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: 4.57). 10/2012; 287(49). DOI: 10.1074/jbc.M112.416545
Source: PubMed


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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    • "Despite these reported discrepancies between mouse and human somatic cells, it is generally agreed that treatment of somatic cells with HDAC inhibitors during reprogramming can induce changes that drive cells toward the pluripotent state due to increased histone acetylation and activation of gene expression. Two recent studies showed that the nucleosome remodeling and deacetylation (NuRD) complex containing HDAC1 and HDAC2 is functionally associated with suppression of pluripotency-associated gene expression and promotion of lineage commitment in mESCs103,104. These studies reiterate the significant role of HDACs in the regulation of cellular pluripotency and suggest that HDACs regulate pluripotency through a mechanism involving chromatin remodeling. "
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