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PMID: 10688650 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

p300 requires its histone acetyltransferase activity and SRC-1 interaction domain to facilitate thyroid hormone receptor activation in chromatin.

Molecular and cellular biology ·Vol. 20 ·No. 6 ·2000-03-00 ·Pages 2031-42

Li J, O'Malley BW, Wong J

Abstract

We have characterized the mechanism by which coactivator p300 facilitates transcriptional activation mediated by the heterodimer of thyroid hormone (T3) receptor and 9-cis retinoid acid receptor (TR-RXR) in the context of chromatin. We demonstrate that, while p300 can enhance the transcriptional activation mediated by both liganded TR-RXR and GAL4-VP16, its histone acetyltransferase activity (HAT) is required for its ability to facilitate liganded TR-RXR- but not GAL4-VP16-mediated transcriptional activation. To understand how p300 is recruited by liganded TR-RXR, we have analyzed the interactions between TR-RXR and p300 as well as SRC-1 family coactivators. We show that, in contrast to a strong hormone-dependent interaction between TR-RXR and SRC-1 family coactivators, p300 displays minimal, if any, T3-dependent interaction with TR-RXR. However, p300 can be recruited by liganded TR-RXR through its interaction with SRC-1 family coactivators. Consistent with the protein-protein interaction profile described above, we demonstrate that the SRC-1 interaction domain of p300 is important for its ability to facilitate transcriptional activation mediated by TR-RXR, whereas its nuclear receptor interaction domain is dispensable. Collectively, these results reveal the functional significance of the HAT activity of p300 and define an indirect mode for the action of p300 in TR-RXR activation.

Keywords
Non-programmatic
MeSH Terms
Acetyltransferases/physiology Animals Chromatin/physiology Gene Expression Regulation/physiology Histone Acetyltransferases Nuclear Proteins/physiology Nuclear Receptor Coactivator 1 Receptors, Thyroid Hormone/physiology Saccharomyces cerevisiae Proteins Signal Transduction Trans-Activators/physiology Transcription Factors/physiology Transcriptional Activation Xenopus
Chemicals
Chromatin Nuclear Proteins Receptors, Thyroid Hormone Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors Acetyltransferases Histone Acetyltransferases Nuclear Receptor Coactivator 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Li J
Department of Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
O'Malley B W
Wong J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.6.2031-2042.2000
Published
2000-03-00
Pages
2031-42
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC110820
Subset
IM
Grants
NIDDK NIH HHS · R01 DK056324 · United States
NIDDK NIH HHS · R01 DK 56324 · United States
External Links
PubMed source DOI: 10.1128/MCB.20.6.2031-2042.2000 PMC Full Text View journal details
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