Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1997-9-2
pubmed:abstractText
Two hormone-responsive segments, one in the region of the promoter and one in intron 1, are identified in two homologous androgen-regulated and differentially expressed rat genes encoding the cystatin-related proteins (CRPs). Footprint analysis with the androgen receptor (AR) DNA-binding domain on the promoter-containing fragments reveals an AR-binding site downstream of the transcription start point in the crp2 gene (ARBSd/crp2, +40/+63). It displays an androgen response element-like sequence motif 5'-AGAAGAaaaTGTACA-3' and overlaps with the ATG translation start codon. A double-stranded oligonucleotide containing this sequence forms a DNA-protein complex with the full-length AR synthesized by vaccinia, as seen in band shift assays. Additional AR-binding sites, ARBSu/crp1 and ARBSu/crp2, occur 5' upstream of the transcription start point and are located at an identical position (-142/ -120) in crp1 and crp2. The AR affinity for these two slightly different sequence motifs is relatively weak. The biological function of all three AR-binding sites as transcription control elements has been studied. The ARBSd/crp2 element clearly shows androgen-response element characteristics. The contribution of the common upstream element to the androgen-dependent control of reporter gene transcription is less clear. The transcription of a reporter gene construct containing the crp2 footprint fragment crp2F (-273/+88) is hormonally regulated as determined by transfection into the human breast cancer cell line T-47D. Androgens, but also glucocorticoids, efficiently stimulate steroid-dependent transcription of the chloramphenicol acetyltransferase gene. Mutation of the 5'-TGTACA-3' sequence in ARBSd/crp2 destroys the AR binding and abolishes the androgen-dependent synthesis of chloramphenicol acetyltransferase. A large fragment derived from intron 1 of the crp1 and crp2 gene can also provide the androgen-dependent transcription of chimeric constructs in T-47D cells. However, the induction measured is less than the one observed with crp2F (-273/+88), and this activity seems to reside in several subfragments that each display a low but consistent androgen responsiveness.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1033-43
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9212051-Androgens, pubmed-meshheading:9212051-Animals, pubmed-meshheading:9212051-Binding Sites, pubmed-meshheading:9212051-Breast Neoplasms, pubmed-meshheading:9212051-Cystatins, pubmed-meshheading:9212051-DNA Footprinting, pubmed-meshheading:9212051-DNA Mutational Analysis, pubmed-meshheading:9212051-Deoxyribonuclease I, pubmed-meshheading:9212051-Electrophoresis, pubmed-meshheading:9212051-Exons, pubmed-meshheading:9212051-Genes, Reporter, pubmed-meshheading:9212051-Humans, pubmed-meshheading:9212051-Male, pubmed-meshheading:9212051-Proteins, pubmed-meshheading:9212051-RNA, Messenger, pubmed-meshheading:9212051-Rats, pubmed-meshheading:9212051-Rats, Wistar, pubmed-meshheading:9212051-Receptors, Androgen, pubmed-meshheading:9212051-Recombinant Proteins, pubmed-meshheading:9212051-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:9212051-Transcription, Genetic, pubmed-meshheading:9212051-Transfection, pubmed-meshheading:9212051-Tumor Cells, Cultured
pubmed:year
1997
pubmed:articleTitle
Identification of a functional androgen-response element in the exon 1-coding sequence of the cystatin-related protein gene crp2.
pubmed:affiliation
Division of Biochemistry, Faculty of Medicine, University of Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't