Thyroid hormone receptor mediates transcriptional activation and repression of different promoters in vitro

Shoumen Datta, Sheela N. Magge, Laird D. Madison, J. Larry Jameson

Research output: Contribution to journalArticlepeer-review

Abstract

The thyroid hormone receptor (TR) has the dual ability to activate or repress transcription of specific genes. A cell-free transcription system was used to study the effects of TR on transcription by positively (TREpMLP) and negatively (TSH α) regulated promoters. Receptor-deficient HeLa cell extracts were complemented with baculovirus-produced TR. TR stimulated transcription from the TREpMLP promoter by 3-fold, and trans-activation did not require hormone. Transcriptional stimulation by TR required the presence of the TRE sequence and was diminished by the addition of competitor TRE binding sites. Baculovirus-produced TR repressed transcription in vitro from the TSH α promoter by 30-50%, also in a hormone-independent manner. Transcription from a control adenovirus 2 major late promoter was unaffected by added TR. Receptor-specific antisera and competition with TRE binding sites impaired TR-mediated repression of the TSH α promoter. Unlike transcriptional stimulation, which was optimal when TR and HeLa extracts were added concomitantly, transcriptional repression by the TR was most effective when the receptor was preincubated with the α-promoter, suggesting that receptor binding to the promoter may block access of other proteins to cause transcriptional repression. These results indicate that baculovirus-expressed TR mediates transcriptional activation and repression in a promoter-specific manner in vitro. This system provides a valuable model for examining transcriptional control by the TR.

Original languageEnglish (US)
Pages (from-to)815-825
Number of pages11
JournalMolecular Endocrinology
Volume6
Issue number5
DOIs
StatePublished - May 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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