MCAF mediates MBD1-dependent transcriptional repression.
DNA methylation is involved in a variety of genome functions, including gene control and chromatin dynamics. MBD1 is a transcriptional regulator through the cooperation of a methyl-CpG binding domain, cysteine-rich CXXC domains, and a transcriptional repression domain. A yeast two-hybrid screen was performed to investigate the role of MBD1 in methylation-based transcriptional repression. We report a mediator, MBD1-containing chromatin-associated factor (MCAF), that interacts with the transcriptional repression domain of MBD1. MCAF harbors two conserved domains that allow it to interact with MBD1 and enhancer-like transactivator Sp1. MCAF possesses a coactivator-like activity, and it seems to facilitate Sp1-mediated transcription. In contrast, the MBD1-MCAF complex blocks transcription through affecting Sp1 on methylated promoter regions. These data provide a mechanistic basis for direct inhibition of gene expression via methylation-dependent and histone deacetylation-resistant processes.
Fujita
Naoyuki
N
Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto University, Kumamoto 860-0811, Japan.
Watanabe
Sugiko
S
Ichimura
Takaya
T
Ohkuma
Yoshiaki
Y
Chiba
Tsutomu
T
Saya
Hideyuki
H
Nakao
Mitsuyoshi
M
D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D020798:Two-Hybrid System Techniques
D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C066141:MBD1 protein, human; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA