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

Thyroid hormone receptors (TRs) regulate transcription by recruiting distin ct coregulatory complexes to target gene promoters. Coactivators implicated in ligand-dependent activation by TR include p300, the CREB-binding protei n (CBP), members of the p160/SRC family, and the multisubunit TR-associated protein (TRAP) complex. Using a stable TR-expressing HeLa cell line, we sh ow 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) follo wing addition of thyroid hormone (T-3). In close agreement with these obser vations, we find that TR is associated with potent histone acetyltransferas e activity rapidly following T-3-treatment. By contrast, we observe that fo rmation of TR-TRAP complexes occurs significantly later (similar to3 h) pos t T-3 treatment. An examination of the kinetics of T-3-induced gene express ion in HeLa cells reveals bimodal or delayed activation on specific T-3-res ponsive promoters. Taken together, our data are consistent with the hypothe sis that T-3-dependent activation at specific target promoters may involve the regulated action of multiple TR-coactivator complexes.