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

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.

• Authors: Brian F Clem, Barbara J Clark
• Journal: Molecular endocrinology (Baltimore, Md.) (Mol Endocrinol) Vol. 20 Issue 1 Pg. 100-13 (Jan 2006) ISSN: 0888-8809 [Print] United States
• PMID: 16109738 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Phosphoproteins
• RNA, Messenger
• Repressor Proteins
• SIN3A transcription factor
• Sp3 protein, mouse
• steroidogenic acute regulatory protein
• Sp3 Transcription Factor
• trichostatin A
• Hdac1 protein, mouse
• Hdac2 protein, mouse
• Histone Deacetylase 1
• Histone Deacetylase 2
• Histone Deacetylases
• Sin3 Histone Deacetylase and Corepressor Complex

Topics

• Animals
• Cell Line, Tumor
• Chromatin Immunoprecipitation
• Gene Expression Regulation
• Genes, Reporter
• Histone Deacetylase 1
• Histone Deacetylase 2
• Histone Deacetylase Inhibitors
• Histone Deacetylases (metabolism)
• Hydroxamic Acids (pharmacology)
• Leydig Cell Tumor
• Male
• Mice
• Mutation
• Phosphoproteins (genetics, metabolism)
• Promoter Regions, Genetic
• Protein Binding
• RNA, Messenger (metabolism)
• Repressor Proteins (antagonists & inhibitors, genetics, metabolism)
• Sin3 Histone Deacetylase and Corepressor Complex
• Sp3 Transcription Factor (metabolism)
• Transcription, Genetic