This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fujita, N.
Right arrow Articles by Nakao, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fujita, N.
Right arrow Articles by Nakao, M.

 Previous Article  |  Next Article 

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

Naoyuki Fujita,1,2,3 Sugiko Watanabe,1 Takaya Ichimura,1 Yoshiaki Ohkuma,4 Tsutomu Chiba,3 Hideyuki Saya,2 and Mitsuyoshi Nakao1*

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.

* Corresponding author. Mailing address: Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. Phone: 81-96-373-6800. Fax: 81-96-373-6804. E-mail: mnakao{at}gpo.kumamoto-u.ac.jp.

Molecular and Cellular Biology, April 2003, p. 2834-2843, Vol. 23, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.8.2834-2843.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Liu, L., Ishihara, K., Ichimura, T., Fujita, N., Hino, S., Tomita, S., Watanabe, S., Saitoh, N., Ito, T., Nakao, M. (2009). MCAF1/AM Is Involved in Sp1-mediated Maintenance of Cancer-associated Telomerase Activity. J. Biol. Chem. 284: 5165-5174 [Abstract] [Full Text]  
  • Misawa, K., Ueda, Y., Kanazawa, T., Misawa, Y., Jang, I., Brenner, J. C., Ogawa, T., Takebayashi, S., Grenman, R. A., Herman, J. G., Mineta, H., Carey, T. E. (2008). Epigenetic Inactivation of Galanin Receptor 1 in Head and Neck Cancer. Clin. Cancer Res. 14: 7604-7613 [Abstract] [Full Text]  
  • Allan, A. M., Liang, X., Luo, Y., Pak, C., Li, X., Szulwach, K. E., Chen, D., Jin, P., Zhao, X. (2008). The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits. Hum Mol Genet 17: 2047-2057 [Abstract] [Full Text]  
  • Sakamoto, Y., Watanabe, S., Ichimura, T., Kawasuji, M., Koseki, H., Baba, H., Nakao, M. (2007). Overlapping Roles of the Methylated DNA-binding Protein MBD1 and Polycomb Group Proteins in Transcriptional Repression of HOXA Genes and Heterochromatin Foci Formation. J. Biol. Chem. 282: 16391-16400 [Abstract] [Full Text]  
  • Olave, I. A., Doneanu, C., Fang, X., Stamatoyannopoulos, G., Li, Q. (2007). Purification and Identification of Proteins That Bind to the Hereditary Persistence of Fetal Hemoglobin -198 Mutation in the {gamma}-Globin Gene Promoter. J. Biol. Chem. 282: 853-862 [Abstract] [Full Text]  
  • Uchimura, Y., Ichimura, T., Uwada, J., Tachibana, T., Sugahara, S., Nakao, M., Saitoh, H. (2006). Involvement of SUMO Modification in MBD1- and MCAF1-mediated Heterochromatin Formation. J. Biol. Chem. 281: 23180-23190 [Abstract] [Full Text]  
  • Jorgensen, H. F., Adie, K., Chaubert, P., Bird, A. P. (2006). Engineering a high-affinity methyl-CpG-binding protein. Nucleic Acids Res 34: e96-e96 [Abstract] [Full Text]  
  • Chang, L.-K., Chung, J.-Y., Hong, Y.-R., Ichimura, T., Nakao, M., Liu, S.-T. (2005). Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1. Nucleic Acids Res 33: 6528-6539 [Abstract] [Full Text]  
  • Jang, J.-S., Lee, S. J., Choi, J. E., Cha, S. I., Lee, E. B., Park, T. I., Kim, C. H., Lee, W. K., Kam, S., Choi, J.-Y., Kang, Y. M., Park, R.-W., Kim, I.-S., Cho, Y. L., Jung, T. H., Han, S. B., Park, J. Y. (2005). Methyl-CpG Binding Domain 1 Gene Polymorphisms and Risk of Primary Lung Cancer. Cancer Epidemiol. Biomarkers Prev. 14: 2474-2480 [Abstract] [Full Text]  
  • Ichimura, T., Watanabe, S., Sakamoto, Y., Aoto, T., Fujita, N., Nakao, M. (2005). Transcriptional Repression and Heterochromatin Formation by MBD1 and MCAF/AM Family Proteins. J. Biol. Chem. 280: 13928-13935 [Abstract] [Full Text]  
  • Jeffery, L., Nakielny, S. (2004). Components of the DNA Methylation System of Chromatin Control Are RNA-binding Proteins. J. Biol. Chem. 279: 49479-49487 [Abstract] [Full Text]  
  • Milutinovic, S., Brown, S. E., Zhuang, Q., Szyf, M. (2004). DNA Methyltransferase 1 Knock Down Induces Gene Expression by a Mechanism Independent of DNA Methylation and Histone Deacetylation. J. Biol. Chem. 279: 27915-27927 [Abstract] [Full Text]  
  • Jorgensen, H. F., Ben-Porath, I., Bird, A. P. (2004). Mbd1 Is Recruited to both Methylated and Nonmethylated CpGs via Distinct DNA Binding Domains. Mol. Cell. Biol. 24: 3387-3395 [Abstract] [Full Text]  
  • BIRD, A., MACLEOD, D. (2004). Reading the DNA Methylation Signal. Cold Spring Harb Symp Quant Biol 69: 113-118 [Abstract]  
  • Watanabe, S., Ichimura, T., Fujita, N., Tsuruzoe, S., Ohki, I., Shirakawa, M., Kawasuji, M., Nakao, M. (2003). Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin. Proc. Natl. Acad. Sci. USA 100: 12859-12864 [Abstract] [Full Text]  
  • Fujita, N., Watanabe, S., Ichimura, T., Tsuruzoe, S., Shinkai, Y., Tachibana, M., Chiba, T., Nakao, M. (2003). Methyl-CpG Binding Domain 1 (MBD1) Interacts with the Suv39h1-HP1 Heterochromatic Complex for DNA Methylation-based Transcriptional Repression. J. Biol. Chem. 278: 24132-24138 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»