Back to Search
Start Over
The Mechanism of Negative Transcriptional Regulation by Thyroid Hormone: Lessons From the Thyrotropin β Subunit Gene
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- Thyroid hormone (T3) activates (positive regulation) or represses (negative regulation) target genes at the transcriptional level. The molecular mechanism of the former has been elucidated in detail; however, the mechanism for negative regulation has not been established. The best example of the gene that is negatively regulated by T3 is the thyrotropin (thyroid-stimulating hormone) β subunit (TSHβ) gene. Analogous to the T3-responsive element (TRE) in positive regulation, a negative TRE (nTRE) has been postulated in the TSHβ gene. However, TSHβ promoter analysis, performed in the presence of transcription factors Pit1 and GATA2, which are determinants of thyrotroph differentiation in the pituitary, revealed that the nTRE is dispensable for inhibition by T3. We propose a tethering model in which the T3 receptor is tethered to GATA2 via protein-protein interaction and inhibits GATA2-dependent transactivation of the TSHβ gene in a T3-dependent manner.
- Subjects :
- 0301 basic medicine
endocrine system
Thyroid hormone receptor
Growth-hormone-releasing hormone receptor
Biology
Molecular biology
Thyroid hormone receptor beta
03 medical and health sciences
Transactivation
030104 developmental biology
Nuclear receptor
Thyroid hormone receptor alpha
Thyrotropin-releasing hormone receptor
Transcriptional regulation
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........19b74193352c752a87bca50303691a90