First Author | Matsui K | Year | 2013 |
Journal | Biochem Biophys Res Commun | Volume | 440 |
Issue | 1 | Pages | 184-9 |
PubMed ID | 24055033 | Mgi Jnum | J:211423 |
Mgi Id | MGI:5575435 | Doi | 10.1016/j.bbrc.2013.09.061 |
Citation | Matsui K, et al. (2013) Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin beta gene promoter. Biochem Biophys Res Commun 440(1):184-9 |
abstractText | The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor beta (TRbeta) on the TSHbeta gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHbeta gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHbeta gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHbeta gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHbeta gene promoter. |