MCAF mediates MBD1-dependent transcriptional repression
- PMID: 12665582
- PMCID: PMC152570
- DOI: 10.1128/MCB.23.8.2834-2843.2003
MCAF mediates MBD1-dependent transcriptional repression
Abstract
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.
Figures
![FIG. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/152570/bin/mb0831804001.gif)
![FIG. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/152570/bin/mb0831804002.gif)
![FIG. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/152570/bin/mb0831804003.gif)
![FIG. 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/152570/bin/mb0831804004.gif)
![FIG. 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/152570/bin/mb0831804005.gif)
Similar articles
-
Transcriptional repression and heterochromatin formation by MBD1 and MCAF/AM family proteins.J Biol Chem. 2005 Apr 8;280(14):13928-35. doi: 10.1074/jbc.M413654200. Epub 2005 Feb 2. J Biol Chem. 2005. PMID: 15691849
-
Mechanism of transcriptional regulation by methyl-CpG binding protein MBD1.Mol Cell Biol. 2000 Jul;20(14):5107-18. doi: 10.1128/MCB.20.14.5107-5118.2000. Mol Cell Biol. 2000. PMID: 10866667 Free PMC article.
-
Active repression of methylated genes by the chromosomal protein MBD1.Mol Cell Biol. 2000 Feb;20(4):1394-406. doi: 10.1128/MCB.20.4.1394-1406.2000. Mol Cell Biol. 2000. PMID: 10648624 Free PMC article.
-
Regulation of transcription and chromatin by methyl-CpG binding protein MBD1.Brain Dev. 2001 Dec;23 Suppl 1:S174-6. doi: 10.1016/s0387-7604(01)00348-5. Brain Dev. 2001. PMID: 11738867 Review.
-
Methyl-CpG-binding proteins. Targeting specific gene repression.Eur J Biochem. 2001 Jan;268(1):1-6. doi: 10.1046/j.1432-1327.2001.01869.x. Eur J Biochem. 2001. PMID: 11121095 Review.
Cited by
-
Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos.EMBO J. 2024 Jul;43(13):2685-2714. doi: 10.1038/s44318-024-00127-z. Epub 2024 Jun 3. EMBO J. 2024. PMID: 38831123 Free PMC article.
-
Keep quiet: the HUSH complex in transcriptional silencing and disease.Nat Struct Mol Biol. 2024 Jan;31(1):11-22. doi: 10.1038/s41594-023-01173-7. Epub 2024 Jan 12. Nat Struct Mol Biol. 2024. PMID: 38216658 Review.
-
Light-Activatable MBD-Readers of 5-Methylcytosine Reveal Domain-Dependent Chromatin Association Kinetics In Vivo.Adv Sci (Weinh). 2024 Mar;11(11):e2307930. doi: 10.1002/advs.202307930. Epub 2024 Jan 2. Adv Sci (Weinh). 2024. PMID: 38164822 Free PMC article.
-
MBD1 protects replication fork stability by recruiting PARP1 and controlling transcription-replication conflicts.Cancer Gene Ther. 2024 Jan;31(1):94-107. doi: 10.1038/s41417-023-00685-0. Epub 2023 Nov 10. Cancer Gene Ther. 2024. PMID: 37949945
-
Mechanomemory in protein diffusivity of chromatin and nucleoplasm after force cessation.Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2221432120. doi: 10.1073/pnas.2221432120. Epub 2023 Mar 21. Proc Natl Acad Sci U S A. 2023. PMID: 36943889 Free PMC article.
References
-
- Bestor, T. H., and G. L. Verdine. 1994. DNA methyltransferases. Curr. Opin. Cell Biol. 6:380-389. - PubMed
-
- Bird, A. 2002. DNA methylation patterns and epigenetic memory. Genes Dev. 16:6-21. - PubMed
-
- Bird, A. P., and A. P. Wolffe. 1999. Methylation-induced repression-belts, braces, and chromatin. Cell 99:451-454. - PubMed
-
- Boyes, J., and A. Bird. 1991. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 64:1123-1134. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials