Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-7-8
pubmed:abstractText
Expression of the GnRH receptor (GnRH-R) gene in the anterior pituitary gland, as with the genes encoding the gonadotropin subunits, is restricted to gonadotrophs. Thus, it is conceivable that a common mechanism is involved in activating cell-specific expression of these genes. In fact, expression of the alpha- and LHbeta-subunit genes appears to require binding of the nuclear orphan receptor, steroidogenic factor-1 (SF-1). Here we have used DNA protein-binding assays to identify a high-affinity binding site for SF-1 in the proximal promoter of the murine GnRH-R gene. Southwestern blot analysis using this site as a radiolabeled probe revealed binding to a 53-kDa protein in alphaT3-1 cell extracts. Furthermore, mutation of this site led to a 58% reduction in promoter activity in the gonadotroph-derived alphaT3-1 cell line. Thus, SF-1 may represent at least one common pathway for gonadotroph-specific gene expression. In addition, we used block-replacement mutagenesis to functionally scan approximately 100 base pairs (bp) in a region that we had previously identified as critical for cell-specific promoter activity. Mutation of a partial palindrome located at -393 bp relative to the start of translation led to a 63% loss of promoter activity. Finally, a region containing both the SF-1 binding site and the -393 site was sufficient to stimulate cell-specific expression from a heterologous, minimal promoter. Thus, we suggest that a complex enhancer that includes a binding site for SF-1 mediates cell-specific expression of the GnRH-R gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-3363
pubmed:author
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
160-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9002645-Animals, pubmed-meshheading:9002645-Binding Sites, pubmed-meshheading:9002645-Cell Line, pubmed-meshheading:9002645-DNA, pubmed-meshheading:9002645-DNA-Binding Proteins, pubmed-meshheading:9002645-Enhancer Elements, Genetic, pubmed-meshheading:9002645-Fushi Tarazu Transcription Factors, pubmed-meshheading:9002645-Gene Expression, pubmed-meshheading:9002645-Homeodomain Proteins, pubmed-meshheading:9002645-Mice, pubmed-meshheading:9002645-Mutagenesis, pubmed-meshheading:9002645-Promoter Regions, Genetic, pubmed-meshheading:9002645-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:9002645-Receptors, LHRH, pubmed-meshheading:9002645-Repetitive Sequences, Nucleic Acid, pubmed-meshheading:9002645-Steroidogenic Factor 1, pubmed-meshheading:9002645-Transcription Factors, pubmed-meshheading:9002645-Transfection
pubmed:year
1997
pubmed:articleTitle
A binding site for steroidogenic factor-1 is part of a complex enhancer that mediates expression of the murine gonadotropin-releasing hormone receptor gene.
pubmed:affiliation
Department of Physiology, College of Veterinary Medicine, Colorado State University, Fort Collins 80523, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.