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| Subject Categories: Chromatin & Transcription |
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| The EMBO Journal
(2005) 24, 336–346, doi:10.1038/sj.emboj.7600509 Published online 16 December 2004 |
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| Myc represses transcription through recruitment of DNA methyltransferase corepressor |
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| Carmen Brenner1, 7, Rachel Deplus1, 7, Céline Didelot1, 7, Axelle Loriot2, Emmanuelle Viré1, Charles De Smet2, Arantxa Gutierrez3, Davide Danovi4, David Bernard1, Thierry Boon2, Pier Giuseppe Pelicci4, Bruno Amati4, Tony Kouzarides5, Yvan de Launoit1, 6, Luciano Di Croce3, 4 and François Fuks1, 5 |
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1 Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, Brussels, Belgium 2 Ludwig Institute For Cancer Research, UCL, Brussels, Belgium 3 ICREA and Center for Genomic Regulation, Barcelona, Spain 4 Department of Experimental Oncology, European Institute of Oncology, Milan, Italy 5 Wellcome/Cancer Research UK Institute and Department of Pathology, University of Cambridge, Cambridge, UK 6 UMR 8117, CNRS Institut Pasteur de Lille, Université de Lille 1, Institut de Biologie de Lille, Lille, Cedex, France To whom correspondence should be addressed François Fuks, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium. Tel.: +32 2 555 6243; Fax: +32 2 555 6257; E-mail: ffuks@ulb.ac.be 7 These authors contributed equally to this work Received 30 April 2004; Accepted 12 November 2004; Published online 16 December 2004. |
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| Abstract |
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| The Myc transcription factor is an essential mediator of cell growth and proliferation through its ability to both positively and negatively regulate transcription. The mechanisms by which Myc silences gene expression are not well understood. The current model is that Myc represses transcription through functional interference with transcriptional activators. Here we show that Myc binds the corepressor Dnmt3a and associates with DNA methyltransferase activity in vivo. In cells with reduced Dnmt3a levels, we observe specific reactivation of the Myc-repressed p21Cip1 gene, whereas the expression of Myc-activated E-boxes genes is unchanged. In addition, we find that Myc can target Dnmt3a selectively to the promoter of p21Cip1. Myc is known to be recruited to the p21Cip1 promoter by the DNA-binding factor Miz-1. Consistent with this, we observe that Myc and Dnmt3a form a ternary complex with Miz-1 and that this complex can corepress the p21Cip1 promoter. Finally, we show that DNA methylation is required for Myc-mediated repression of p21Cip1. Our data identify a new mechanism by which Myc can silence gene expression not only by passive functional interference but also by active recruitment of corepressor proteins. Furthermore, these findings suggest that targeting of DNA methyltransferases by transcription factors is a wide and general mechanism for the generation of specific DNA methylation patterns within a cell. |
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| Keywords: DNA methylation, Dnmt3a, Myc, transcriptional repression |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Immunology News and Views (01 Oct 2005) Uniting the paths to gene silencing Nature Genetics News and Views (01 Nov 2002) RESEARCHA ribosomal protein L23-nucleophosmin circuit coordinates Miz1 function with cell growth Nature Cell Biology Article (01 Sep 2008) Oncogene Scientific Correspondence |
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