Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter
| Autor: | Norinaga Urahama, Robert G. Roeder, Shumpei Mizuta, Ruri Ishino, Keiji Matsui, Kasumi Oda, Natsumi Hasegawa, Mitsuhiro Ito |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Transcriptional Activation endocrine system Biophysics Mediator Complex Subunit 1 Thyrotropin beta Subunit Biology Biochemistry Article Cell Line MED1 Mice Mediator Transcription (biology) Coactivator Animals Humans Promoter Regions Genetic Molecular Biology Thyroid hormone receptor Promoter Cell Biology Molecular biology GATA2 Transcription Factor Mice Inbred C57BL Nuclear receptor coactivator 1 Protein Subunits Mutation Triiodothyronine Female Transcription Factor Pit-1 |
| Zdroj: | Biochemical and Biophysical Research Communications. 440:184-189 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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