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) |