Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
1999-12-29
pubmed:abstractText
The growth hormone (GH) receptor is essential for the actions of growth hormone on postnatal growth and metabolism. GH receptor transcripts are characterized by the presence of disparate 5'-untranslated exons. Factors regulating the expression of the GC rich L2 transcript of the murine GH receptor gene have hitherto remained unidentified. To characterize the mechanisms regulating expression of the L2 transcript, primer extension and ribonuclease protection assays were used to identify transcription start sites in RNA from liver of adult mice. Transient transfection experiments revealed that 2.0 kilobase pairs of the L2 5'-flanking sequence exhibited promoter activity in BNL CL.2 (mouse liver) cells, CV-1 (monkey kidney) cells, and HRP.1 trophoblasts. Deletional analysis localized a major regulatory region to within 75 base pairs of the 5' transcription start site. Sequence analysis revealed that the region contained consensus binding sites for the Sp family of transcription factors. Standard gel shift and supershift analysis using liver nuclear extracts established that Sp1 and Sp3 bound this regulatory element. Transfection of wild type but not mutant decoy oligonucleotides into BNL CL.2 cells decreased the activity of the L2 promoter. Overexpression of Sp1 and Sp3 protein in Drosophila Schneider cells established that Sp3 is more potent than Sp1 in transactivating the L2 promoter. Co-transfection experiments further established that Sp1 antagonizes the activity of Sp3 to transactivate the L2 promoter. Western blot analysis of liver nuclear extracts revealed that the levels of Sp3 increase significantly after birth, suggesting a role for the Sp family of transcription factors in controlling the fetal to postnatal increase in GH receptor gene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34327-36
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10567409-Animals, pubmed-meshheading:10567409-Base Sequence, pubmed-meshheading:10567409-Binding Sites, pubmed-meshheading:10567409-Cell Line, pubmed-meshheading:10567409-DNA-Binding Proteins, pubmed-meshheading:10567409-Gene Expression Regulation, Developmental, pubmed-meshheading:10567409-Liver, pubmed-meshheading:10567409-Luciferases, pubmed-meshheading:10567409-Mice, pubmed-meshheading:10567409-Molecular Sequence Data, pubmed-meshheading:10567409-Mutation, pubmed-meshheading:10567409-Promoter Regions, Genetic, pubmed-meshheading:10567409-Protein Binding, pubmed-meshheading:10567409-Receptors, Somatotropin, pubmed-meshheading:10567409-Recombinant Fusion Proteins, pubmed-meshheading:10567409-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:10567409-Sp1 Transcription Factor, pubmed-meshheading:10567409-Sp3 Transcription Factor, pubmed-meshheading:10567409-Transcription, Genetic, pubmed-meshheading:10567409-Transcription Factors
pubmed:year
1999
pubmed:articleTitle
Role of the Sp family of transcription factors in the ontogeny of growth hormone receptor gene expression.
pubmed:affiliation
Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't