Nucleic Acids Research Advance Access originally published online on February 20, 2007
Nucleic Acids Research 2007 35(5):1687-1697; doi:10.1093/nar/gkl1141
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Nucleic Acids Research, 2007, Vol. 35, No. 5 1687-1697
© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Ovol1 represses its own transcription by competing with transcription activator c-Myb and by recruiting histone deacetylase activity
1Department of Biological Chemistry, School of Medicine, 2Developmental Biology Center, University of California, Irvine, CA 92697, USA and 3Department of Biochemistry, State University of New York at Buffalo, New York, USA
*To whom correspondence should be addressed. Tel: +1 949 824 3101; Fax: +1 949 824 2688; Email: xdai{at}uci.edu
Received October 30, 2006. Revised December 13, 2006. Accepted December 14, 2006.
Ovol1 belongs to a family of evolutionarily conserved zinc finger proteins that act downstream of key developmental signaling pathways such as Wnt and TGF-ß/BMP. It plays important roles in epithelial and germ cell development, particularly by repressing c-Myc and Id2 genes and modulating the balance between proliferation and differentiation of progenitor cells. In this study, we show that Ovol1 negatively regulates its own expression by binding to and repressing the activity of its promoter. We further demonstrate that Ovol1 uses both passive and active repression mechanisms to auto-repress: (1) it antagonizes transcriptional activation of c-Myb, a known positive regulator of proliferation, by competing for DNA binding; (2) it recruits histone deacetylase activity to the promoter via an N-terminal SNAG repressor domain. At Ovol1 cognate sites in the endogenous Ovol1 promoter, c-Myb binding correlates with increased histone acetylation, whereas the expression of Ovol1 correlates with a displacement of c-Myb from the DNA and decreased histone acetylation. Collectively, our data suggest that Ovol1 restricts its own expression by counteracting c-Myb activation and histone acetylation of the Ovol1 promoter.