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 (approximately 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 (approximately 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.
Sharma
D
D
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
Fondell
J D
JD
D000123:Acetyltransferases / Q000378:metabolism*; D050882:CREB-Binding Protein; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D056913:Mediator Complex Subunit 1; D009687:Nuclear Proteins / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D046911:Macromolecular Substances; D056913:Mediator Complex Subunit 1; D009687:Nuclear Proteins; D056920:Nuclear Receptor Coactivator 1; D011988:Receptors, Thyroid Hormone; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014284:Triiodothyronine; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C538855:MED1 protein, human; C494363:CREBBP protein, human; C538859:NCOA1 protein, human