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.
Mesh Terms:
Binding Sites, Cell Line, Chemokine CCL2, DNA, DNA Methylation, DNA-Binding Proteins, Enzyme Inhibitors, Hela Cells, Histone Deacetylase Inhibitors, Humans, Promoter Regions, Genetic, Protein Structure, Tertiary, Recombinant Proteins, Repressor Proteins, Transcription Factors, Transcription, Genetic, Two-Hybrid System Techniques
Binding Sites, Cell Line, Chemokine CCL2, DNA, DNA Methylation, DNA-Binding Proteins, Enzyme Inhibitors, Hela Cells, Histone Deacetylase Inhibitors, Humans, Promoter Regions, Genetic, Protein Structure, Tertiary, Recombinant Proteins, Repressor Proteins, Transcription Factors, Transcription, Genetic, Two-Hybrid System Techniques
Mol. Cell. Biol.
Date: Apr. 01, 2003
PubMed ID: 12665582
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