Source:http://linkedlifedata.com/resource/pubmed/id/17761951
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2007-11-28
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pubmed:abstractText |
Cofactors modulate nuclear receptor activity and impact human health and disease, yet surprisingly little is known about their transcriptional regulation. Androgen receptor trapped clone-27 (ART-27) is a cofactor that binds to androgen receptor (AR) amino terminus and modulates AR-dependent transcription. Interestingly, ART-27 displays both a cell type- and developmental stage-specific expression pattern. However, the cis-acting elements and trans-acting factors affecting ART-27 gene expression have not been elucidated. We found that ART-27 gene expression is repressed and its promoter is histone H3-K27 tri-methylated in human embryonic kidney cells, but not prostate cells, and the histone deacetylase inhibitor, trichostatin A, relieves this inhibition. The DNA response elements that control the induction of ART-27 gene expression were also characterized. The major cis-acting element corresponds to a consensus cAMP-responsive element (CRE) and binds the CRE-binding protein (CREB) as shown by EMSA and chromatin immunoprecipitation assays. Furthermore, ART-27 promoter activity is induced upon CREB overexpression. Epidermal growth factor, which activates CREB via phosphorylation, also induces ART-27 expression, whereas a reduction in CREB phosphorylation or expression blocks this induction in prostate cells. In human prostate development, both epithelial and stromal cells express CREB; however, active phosphorylated CREB is restricted to epithelial cells where ART-27 is expressed. Based on these findings, we propose a transcriptional regulatory circuit for the developmental expression of ART-27 that includes repression by chromatin modification through a trichostatin A-sensitive factor and activation upon growth factor stimulation via CREB.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/UXT protein, human
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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 |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2864-76
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17761951-Cell Line,
pubmed-meshheading:17761951-Gene Expression Regulation,
pubmed-meshheading:17761951-Histones,
pubmed-meshheading:17761951-Humans,
pubmed-meshheading:17761951-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:17761951-Male,
pubmed-meshheading:17761951-Molecular Sequence Data,
pubmed-meshheading:17761951-Neoplasm Proteins,
pubmed-meshheading:17761951-Phosphoserine,
pubmed-meshheading:17761951-Promoter Regions, Genetic,
pubmed-meshheading:17761951-Prostate,
pubmed-meshheading:17761951-Protein Binding,
pubmed-meshheading:17761951-Response Elements,
pubmed-meshheading:17761951-Transcription, Genetic
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pubmed:year |
2007
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pubmed:articleTitle |
Transcriptional regulation of the androgen receptor cofactor androgen receptor trapped clone-27.
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pubmed:affiliation |
Department of Microbiology, 550 First Avenue, New York, New York 10016, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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