scholarly journals The In Vitro Functional Impairment of Thyroid Hormone Receptor Alpha 1 Isoform Mutants Is Mainly Dictated by Reduced Ligand Sensitivity

Thyroid ◽  
2019 ◽  
Vol 29 (12) ◽  
pp. 1834-1842 ◽  
Author(s):  
Karn Wejaphikul ◽  
Anja L.M. van Gucht ◽  
Stefan Groeneweg ◽  
W. Edward Visser ◽  
Theo J. Visser ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Functional Impairment ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Receptor Alpha ◽  
Ligand Sensitivity

scholarly journals Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression.

1996 ◽  
Vol 16 (1) ◽  
pp. 281-287 ◽  
Author(s):  
J D Fondell ◽  
F Brunel ◽  
K Hisatake ◽  
R G Roeder
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Transcriptional Repression ◽  
Thyroid Hormone Receptor ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Human Thyroid ◽  
Terminal Ligand ◽  
Receptor Alpha

Unliganded human thyroid hormone receptor alpha (hTR alpha) can repress transcription by inhibiting the formation of a functional preinitiation complex (PIC) on promoters bearing thyroid hormone receptor (TR)-binding elements. Here we demonstrate that hTR alpha directly contacts the TATA-binding protein (TBP) and that preincubation of hTR alpha with TBP completely alleviates TR-mediated repression in vitro. Using stepwise preassembled PICs, we show that hTR alpha targets either the TBP/TFIIA or the TBP/TFIIA/TFIIB steps of PIC assembly for repression. We also show that the repression domain of hTR alpha maps to the C-terminal ligand-binding region and that direct TR-TBP interactions can be inhibited by thyroid hormone. Together, these results suggest a model in which unliganded hTR alpha contacts promoter-bound TBP and interferes with later steps in the initiation of transcription.

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