Source:http://linkedlifedata.com/resource/pubmed/id/16051668
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2005-11-24
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| pubmed:abstractText |
Transcriptional activation of estrogen receptor alpha (ERalpha) is regulated by the ligand-dependent activation function 2 and the constitutively active N-terminal activation function 1. To identify ERalpha N-terminal-specific coregulators, we screened a breast cDNA library by T7 phage display and isolated histone deacetylase 4 (HDAC4). HDAC4 interacts with the ERalpha N terminus both in vitro and in vivo. Presence of the ERalpha DNA binding domain and hinge region reduce HDAC4 recruitment whereas full-length ERalpha enhances recruitment. HDAC4 interaction is selective for the ERalpha and not ERbeta N terminus and occurs in the nucleus. We demonstrate in vivo that HDAC4 is recruited by the N terminus to the promoter of an endogenous estrogen responsive gene. HDAC4 suppresses transcriptional activation of ERalpha by estrogen and selective ER modulators (SERMs) such as tamoxifen in a cell type-dependent manner. Consistently, silencing of HDAC4 promotes the agonist effect of SERMs (tamoxifen and raloxifene) in a cell type-specific manner. These findings indicate a role for HDAC4 in regulating ERalpha activity as a novel N-terminal coregulator and uncover a mechanism by which certain cell types regulate SERM behavior.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogens,
http://linkedlifedata.com/resource/pubmed/chemical/HDAC4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Selective Estrogen Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0888-8809
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
19
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2930-42
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16051668-Amino Acid Sequence,
pubmed-meshheading:16051668-Animals,
pubmed-meshheading:16051668-Cell Nucleus,
pubmed-meshheading:16051668-Cells, Cultured,
pubmed-meshheading:16051668-Estrogen Receptor alpha,
pubmed-meshheading:16051668-Estrogens,
pubmed-meshheading:16051668-Gene Library,
pubmed-meshheading:16051668-Histone Deacetylases,
pubmed-meshheading:16051668-Humans,
pubmed-meshheading:16051668-Molecular Sequence Data,
pubmed-meshheading:16051668-Promoter Regions, Genetic,
pubmed-meshheading:16051668-Protein Interaction Mapping,
pubmed-meshheading:16051668-Protein Structure, Tertiary,
pubmed-meshheading:16051668-Repressor Proteins,
pubmed-meshheading:16051668-Selective Estrogen Receptor Modulators,
pubmed-meshheading:16051668-Tamoxifen,
pubmed-meshheading:16051668-Transcription, Genetic,
pubmed-meshheading:16051668-Transcriptional Activation
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| pubmed:year |
2005
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| pubmed:articleTitle |
Recruitment of histone deacetylase 4 to the N-terminal region of estrogen receptor alpha.
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| pubmed:affiliation |
The Ben May Institute for Cancer Research, The University of Chicago, Center for Integrative Sciences, Room W330, 929 East 57th Street, Chicago, IL 60637, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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