Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo.
Transcriptional coactivators implicated in gene activation by the thyroid hormone receptor (TR) include members of the p160/steroid receptor coactivator (SRC) family of proteins, p300, and the multisubunit TR-associated protein (TRAP)/Mediator complex. We investigated the temporal recruitment of these cofactors to mammalian thyroid hormone (T3)-responsive promoters in vivo. We show that upon T3 treatment, TR recruits all three types of coactivators to specific promoters in at least two sequential steps: p160/SRC proteins and p300 are recruited first and rapidly induce histone acetylation, followed by the recruitment of the TRAP/Mediator complex. Interestingly, inhibition of histone deacetylase activity with trichostatin A elicited a more rapid promoter recruitment of the TRAP/Mediator complex but not p160/SRC proteins. T3-dependent gene expression assays indicate that all three coactivators are targeted to a promoter before significant activation occurs. These findings thus suggest that histone acetylation may be a prerequisite for TRAP/Mediator recruitment and function at specific T3-responsive mammalian promoters.
Sharma
Dipali
D
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Fondell
Joseph D
JD
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics; D056913:Mediator Complex Subunit 1; D010902:Pituitary Gland; D011401:Promoter Regions, Genetic; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014284:Triiodothyronine / Q000235:genetics*
D002352:Carrier Proteins; D017931:DNA Primers; C538855:MED1 protein, human; C538857:Med1 protein, rat; D056913:Mediator Complex Subunit 1; D011988:Receptors, Thyroid Hormone; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014284:Triiodothyronine; D007453:Iodide Peroxidase; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human