| First Author | Clem BF | Year | 2006 |
| Journal | Mol Endocrinol | Volume | 20 |
| Issue | 1 | Pages | 100-13 |
| PubMed ID | 16109738 | Mgi Jnum | J:104060 |
| Mgi Id | MGI:3611097 | Doi | 10.1210/me.2004-0495 |
| Citation | Clem BF, et al. (2006) Association of the mSin3A-histone deacetylase 1/2 corepressor complex with the mouse steroidogenic acute regulatory protein gene. Mol Endocrinol 20(1):100-13 |
| abstractText | 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. |
