Ovol1 represses its own transcription by competing with transcription activator c-Myb and by recruiting histone deacetylase activity.
Ovol1 belongs to a family of evolutionarily conserved zinc finger proteins that act downstream of key developmental signaling pathways such as Wnt and TGF-beta/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.
Nair
Mahalakshmi
M
Department of Biological Chemistry, School of Medicine, Developmental Biology Center, University of California, Irvine, CA 92697, USA.
Bilanchone
Virginia
V
Ortt
Kori
K
Sinha
Satrajit
S
Dai
Xing
X
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D020598:Proto-Oncogene Proteins c-myb / Q000037:antagonists & inhibitors*; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D006657:Histones; C490318:Ovo1 protein, mouse; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D006655:Histone Deacetylases