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  • 标题:Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo
  • 本地全文:下载
  • 作者:Dipali Sharma ; Joseph D. Fondell
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2002
  • 卷号:99
  • 期号:12
  • 页码:7934-7939
  • DOI:10.1073/pnas.122004799
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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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