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National Institute of Environmental Health Sciences

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Publication Detail

Title: Association of the mSin3A-histone deacetylase 1/2 corepressor complex with the mouse steroidogenic acute regulatory protein gene.

Authors: Clem, Brian F; Clark, Barbara J

Published In Mol Endocrinol, (2006 Jan)

Abstract: 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.

PubMed ID: 16109738 Exiting the NIEHS site

MeSH Terms: Animals; Cell Line, Tumor; Chromatin Immunoprecipitation; Gene Expression Regulation; Genes, Reporter; Histone Deacetylases/antagonists & inhibitors; Histone Deacetylases/metabolism*; Hydroxamic Acids/pharmacology; Leydig Cell Tumor; Male; Mice; Mutation; Phosphoproteins/genetics; Phosphoproteins/metabolism*; Promoter Regions (Genetics); Protein Binding; RNA, Messenger/metabolism; Repressor Proteins/antagonists & inhibitors; Repressor Proteins/genetics; Repressor Proteins/metabolism*; Sp3 Transcription Factor/metabolism; Transcription, Genetic

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