Association of the mSin3A-histone deacetylase 1/2 corepressor complex with the mouse steroidogenic acute regulatory protein gene.
Several factors have been identified in the transcriptional repression of the steroidogenic acute regulatory protein (StAR) gene promoter; yet, no associating corepressor complexes have been characterized for the mouse promoter in MA-10 mouse Leydig tumor cells. We now report that Sp3, CAGA element binding proteins, and a corepressor complex consisting ... of mSin3A, histone deacetylase (HDAC)1, and HDAC2 associates with a transcriptional repressor region within the mouse StAR promoter. 5'-Promoter deletion analysis localized the negative regulatory region between -180 and -150 bp upstream of the transcription start site, and mutations in both the CAGA and Sp binding elements were required to relieve the repression of basal StAR promoter activity. Protein-DNA binding analysis revealed Sp3 and specific CAGA element-binding protein(s) associated with the repressor region. Coimmunoprecipitation analysis identified the presence of the mSin3A, HDAC1, and HDAC2 corepressor complex in MA-10 cells. Furthermore, chromatin immunoprecipitation assays revealed Sp3, mSin3A, and HDAC1/2 association with the proximal region of the StAR promoter in situ. In addition, HDAC inhibition resulted in a dose-dependent activation of a mouse StAR reporter construct, whereas mutations within the repressor region diminished this effect by 44%. In sum, these data support a novel regulatory mechanism for transcriptional repression of the mouse StAR promoter by DNA binding of Sp3 and CAGA element-binding proteins, and association of the Sin3 corepressor complex exhibiting HDAC activity.
Mesh Terms:
Animals, Cell Line, Tumor, Chromatin Immunoprecipitation, Gene Expression Regulation, Genes, Reporter, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Histone Deacetylases, Hydroxamic Acids, Leydig Cell Tumor, Male, Mice, Mutation, Phosphoproteins, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Repressor Proteins, Sp3 Transcription Factor, Transcription, Genetic
Animals, Cell Line, Tumor, Chromatin Immunoprecipitation, Gene Expression Regulation, Genes, Reporter, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Histone Deacetylases, Hydroxamic Acids, Leydig Cell Tumor, Male, Mice, Mutation, Phosphoproteins, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Repressor Proteins, Sp3 Transcription Factor, Transcription, Genetic
Mol. Endocrinol.
Date: Jan. 01, 2006
PubMed ID: 16109738
View in: Pubmed Google Scholar
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