Temporal formation of distinct thyroid hormone receptor coactivator complexes in HeLa cells

Dipali Sharma, Joseph D. Fondell

Research output: Contribution to journalArticle

Abstract

Thyroid hormone receptors (TRs) regulate transcription by recruiting distinct coregulatory complexes to target gene promoters. Coactivators implicated in ligand-dependent activation by TR include p300, the CREB-binding protein (CBP), members of the p160/SRC family, and the multi-subunit TR-associated protein (TRAP) complex. Using a stable TR-expressing HeLa cell line, we show that interaction of TR with members of the p160/SRC family, CBP, and the p300/CBP-associated factor (PCAF) occurs rapidly (∼10 min) following addition of thyroid hormone (T3). In close agreement with these observations, we find that TR is associated with potent histone acetyltransferase activity rapidly following T3-treatment. By contrast, we observe that formation of TR-TRAP complexes occurs significantly later (∼3 h) post T3 treatment. An examination of the kinetics of T3-induced gene expression in HeLa cells reveals bimodal or delayed activation on specific T3-responsive promoters. Taken together, our data are consistent with the hypothesis that T3-dependent activation at specific target promoters may involve the regulated action of multiple TR-coactivator complexes.

Original languageEnglish (US)
Pages (from-to)2001-2009
Number of pages9
JournalMolecular Endocrinology
Volume14
Issue number12
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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