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PMID: 10449719 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin.

Liu Z, Wong J, Tsai SY, Tsai MJ, O'Malley BW

Abstract

Progesterone receptor (PR) functions as a transcription factor that modulates the transcription of target genes in response to progesterone and other signals. The transcriptional activity of PR requires the involvement of coactivators such as steroid receptor coactivator-1 (SRC-1). To dissect the role of SRC-1 in PR transactivation, we established an in vitro transcription system with chromatin templates, in which PR induced transcription in a ligand-dependent and PRE-dependent manner. In the presence of ligand, purified PR bound to chromatin templates, resulting in chromatin remodeling. With this system, the ability of purified SRC-1 to act as a coactivator of PR was examined. SRC-1 potentiated transcription by ligand-activated PR, whereas it had no effect on transcription in the absence of ligands. As SRC-1 possesses intrinsic histone acetyltransferase activity, we tested the role of acetylation in PR-mediated transcription by using a histone deacetylase inhibitor, trichostatin A (TSA). We found that addition of TSA strongly enhanced PR-dependent transcription on chromatin but not on naked DNA template, and the effects of SRC-1 and TSA on PR transactivation were partially redundant. In addition, SRC-1 was able to potentiate PR transactivation with nonchromatin templates. Thus, our results substantiate a two-step mechanism whereby recruitment of coactivator SRC-1 by the ligand-activated PR in vivo leads to (i) chromatin remodeling through histone acetylation and (ii) recruitment/stabilization of the preinitiation complex.

MeSH Terms
Animals Baculoviridae Chromatin/genetics Electrophoresis, Polyacrylamide Gel Histone Acetyltransferases Histone Deacetylase Inhibitors Humans Hydroxamic Acids/pharmacology Ligands Nuclear Receptor Coactivator 1 Receptors, Progesterone/metabolism Spodoptera Trans-Activators/metabolism Transcription Factors/metabolism Transcription, Genetic Xenopus
Chemicals
Chromatin Histone Deacetylase Inhibitors Hydroxamic Acids Ligands Receptors, Progesterone Trans-Activators Transcription Factors trichostatin A Histone Acetyltransferases NCOA1 protein, human Nuclear Receptor Coactivator 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Liu Z
Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Wong J
Tsai S Y
Tsai M J
O'Malley B W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-08-17
Pages
9485-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22235
Subset
IM
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