期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 99, 期 12, 页码 7934-7939出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.122004799
关键词
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资金
- NIDDK NIH HHS [DK 54030-03, R01 DK054030] Funding Source: Medline
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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