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

• DOI: 10.1074/jbc.m112.416545
• Publication Date: 2012-10-18T13:10:04Z
• Authors: Jeffrey J. Kim; Omar Khalid; Sheynie Vo; Ho-hyun Sun; David T.W. Wong; Yong Kim
• Keywords: 0301 basic medicine; Models, Genetic; Transcription, Genetic; Gene Expression Profiling; Stem Cells; Tumor Suppressor Proteins; DNA Methylation; Models, Biological; Epigenesis, Genetic; Nucleosomes; DNA-Binding Proteins; Wnt Proteins; Mice; 03 medical and health sciences; Phenotype; Animals; Promoter Regions, Genetic; Protein Kinases; Embryonic Stem Cells; Gene Deletion; Signal Transduction; Transcription Factors

The 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 signaling genes. The occupancy of MBD3 on several promoters of Wnt genes was significantly lost in the absence of CDK2AP1, resulting in hyperactivation of Wnt. We propose that the transcriptional modulation of the Wnt pathway mediated by NuRD requires the presence of essential auxiliary components such as CDK2AP1, which may aid the association of the complex with specific focal regions of the target promoters.