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Molecular and Cellular Biology, April 2003, p. 2834-2843, Vol. 23, No. 8
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.8.2834-2843.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

MCAF Mediates MBD1-Dependent Transcriptional Repression

Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics,¹ Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Kumamoto University, Kumamoto 860-0811,² Division of Gastroenterology, Department of Internal Medicine, Kyoto University Post Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507,³ Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan⁴

Received 2 December 2002/ Accepted 28 January 2003

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.

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