A novel regulatory factor recruits the nucleosome remodeling complex to wingless integrated (Wnt) signaling gene promoters in mouse embryonic stem cells.
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.
Laboratory of Stem Cell and Cancer Epigenetic Research, UCLA, Los Angeles, California 90095, USA.
Jeffrey J
JJ
Kim
Omar
O
Khalid
Sheynie
S
Vo
Ho-hyun
HH
Sun
David T W
DT
Wong
Yong
Y
Kim
D000818:Animals; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology*; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D020869:Gene Expression Profiling; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D009707:Nucleosomes / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; C492013:Mbd3 protein, mouse; D009707:Nucleosomes; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D011494:Protein Kinases; C496849:Cdk2ap1 protein, mouse