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. 1996 Jan;16(1):281–287. doi: 10.1128/mcb.16.1.281

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

J D Fondell 1, F Brunel 1, K Hisatake 1, R G Roeder 1
PMCID: PMC231001  PMID: 8524305

Abstract

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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Selected References

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