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PMID: 12727881 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription.

The EMBO journal ·Vol. 22 ·No. 9 ·2003-05-01 ·Pages 2146-55

Huang ZQ, Li J, Sachs LM, Cole PA, Wong J

Abstract

Transcriptional activation from chromatin by nuclear receptors (NRs) requires multiple cofactors including CBP/p300, SWI/SNF and Mediator. How NRs recruit these multiple cofactors is not clear. Here we show that activation by androgen receptor and thyroid hormone receptor is associated with the promoter targeting of SRC family members, p300, SWI/SNF and the Mediator complex. We show that recruitment of SWI/SNF leads to chromatin remodeling with altered DNA topology, and that both SWI/SNF and p300 histone acetylase activity are required for hormone-dependent activation. Importantly, we show that both the SWI/SNF and Mediator complexes can be targeted to chromatin by p300, which itself is recruited through interaction with SRC coactivators. Furthermore, histone acetylation by CBP/p300 facilitates the recruitment of SWI/SNF and Mediator. Thus, our data indicate that multiple cofactors required for activation are not all recruited through their direct interactions with NRs and underscore a role of cofactor-cofactor interaction and histone modification in coordinating the recruitment of multiple cofactors.

MeSH Terms
Acetylation Amino Acid Sequence Animals Chromatin/metabolism Chromosomal Proteins, Non-Histone/physiology Histones/metabolism Ligands Molecular Sequence Data Nuclear Proteins/metabolism Receptors, Androgen/physiology Receptors, Thyroid Hormone/physiology Trans-Activators/metabolism Transcription Factors/physiology Transcription, Genetic/physiology Tumor Cells, Cultured Xenopus
Chemicals
Chromatin Chromosomal Proteins, Non-Histone Histones Ligands Nuclear Proteins Receptors, Androgen Receptors, Thyroid Hormone SWI-SNF-B chromatin-remodeling complex Trans-Activators Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Huang Zhi-Qing
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Li Jiwen
Sachs Laurent M
Cole Philip A
Wong Jiemin
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg219
Published
2003-05-01
Pages
2146-55
Language
English
Region
England
NLM ID
8208664
PMCID
PMC156091
Subset
IM
Grants
NIDDK NIH HHS · R01 DK056324 · United States
NIDDK NIH HHS · DK56324 · United States
External Links
PubMed source DOI: 10.1093/emboj/cdg219 PMC Full Text View journal details
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