Abstract
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.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:46 a.m.) |
Deposited | 3 years, 4 months ago (April 12, 2022, 10:18 p.m.) |
Indexed | 1 day, 20 hours ago (Aug. 31, 2025, 6:19 a.m.) |
Issued | 23 years, 3 months ago (May 28, 2002) |
Published | 23 years, 3 months ago (May 28, 2002) |
Published Online | 23 years, 3 months ago (May 28, 2002) |
Published Print | 23 years, 2 months ago (June 11, 2002) |
@article{Sharma_2002, title={Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.122004799}, DOI={10.1073/pnas.122004799}, number={12}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sharma, Dipali and Fondell, Joseph D.}, year={2002}, month=may, pages={7934–7939} }