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

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 multisubunit 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 (similar to 10 min) following addition of thyroid hormone (T-3). In close agreement with these observations, we find that TR is associated with potent histone acetyltransferase activity rapidly following T-3-treatment. By contrast, we observe that formation of TR-TRAP complexes occurs significantly later (similar to3 h) post T-3 treatment. An examination of the kinetics of T-3-induced gene expression in HeLa cells reveals bimodal or delayed activation on specific T-3-responsive promoters. Taken together, our data are consistent with the hypothesis that T-3-dependent activation at specific target promoters may involve the regulated action of multiple TR-coactivator complexes.