Open AccessUnliganded Thyroid Hormone Receptor α Can Target TATA-Binding Protein for Transcriptional Repression
Author(s) -
Joseph D. Fondell,
Franck Brunel,
Koji Hisatake,
Robert G. Roeder
Publication year - 1996
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.16.1.281
Subject(s) - tata binding protein , tata box binding protein , psychological repression , thyroid hormone receptor , transcription factor ii a , transcription factor ii b , biology , tata box , promoter , microbiology and biotechnology , transcription preinitiation complex , thyroid hormone receptor alpha , thyroid hormone receptor beta , transcription (linguistics) , nuclear receptor , transcription factor , hormone receptor , dna binding protein , receptor , genetics , gene , gene expression , linguistics , philosophy , cancer , breast cancer
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.