RRC ID 44657
著者 Matsui K, Oda K, Mizuta S, Ishino R, Urahama N, Hasegawa N, Roeder RG, Ito M.
タイトル Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter.
ジャーナル Biochem Biophys Res Commun
Abstract 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 β (TRβ) on the TSHβ 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. TSHβ 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 TSHβ gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHβ 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 TSHβ gene promoter.
巻・号 440(1)
ページ 184-9
公開日 2013-10-11
DOI 10.1016/j.bbrc.2013.09.061
PII S0006-291X(13)01542-8
PMID 24055033
PMC PMC4388257
MeSH Animals Cell Line Female GATA2 Transcription Factor / metabolism Humans Male Mediator Complex Subunit 1 / genetics Mediator Complex Subunit 1 / metabolism* Mice Mice, Inbred C57BL Mutation Promoter Regions, Genetic* Protein Subunits / genetics Protein Subunits / metabolism Thyrotropin, beta Subunit / genetics* Transcription Factor Pit-1 / metabolism Transcriptional Activation* Triiodothyronine / metabolism*
IF 2.985
引用数 1
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS
リソース情報
ヒト・動物細胞 CV-1(RCB0160)