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Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active
J D Fondell1, A L Roy, R G Roeder
1Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021.
Genes & Development
|July 1, 1993
Summary
Unliganded thyroid hormone receptor (TR) actively represses transcription by interfering with preinitiation complex assembly. Ligand binding induces a conformational change, relieving this repression.
Area of Science:
- Molecular Biology
- Gene Regulation
- Endocrinology
Background:
- Thyroid hormone receptor (TR) is a nuclear receptor superfamily member.
- Unliganded TR typically acts as a constitutive repressor of transcription.
Purpose of the Study:
- To investigate the molecular mechanism of TR-mediated transcriptional repression.
- To determine if TR repression is an active or passive process.
Main Methods:
- In vitro transcription assays using HeLa nuclear extracts and purified basal transcription factors.
- Analysis of TR repression in the presence and absence of thyroid hormone (T3) analogs.
Main Results:
- Unliganded TR functions as an active transcriptional repressor, not a passive competitor.
- TR repression involves the basal transcription machinery and occurs independently of known cofactors.
- TR inhibits transcription initiation during preinitiation complex assembly.
Conclusions:
- TR's repressor function is conformationally regulated by ligand binding.
- TR actively interferes with the early stages of transcription initiation.