Linked Life Data

8068205

Source:http://linkedlifedata.com/resource/pubmed/id/8068205

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1994-9-29
pubmed:databankReference
pubmed:abstractText
The cytochrome P450 gene CYP2C11, expressed in the liver of male rats, is transcriptionally regulated in a dual fashion by the sexually dimorphic secretion pattern of growth hormone. To enable analysis of transcriptional regulatory DNA elements, rat genomic sequences were cloned. DNase I hypersensitivity analysis of rat liver nuclei revealed the existence of two hypersensitive sites whose presence in the vicinity of the transcription start site correlates to high transcriptional activity of the gene. Deletion mutants of the 5' flank were fused to reporter genes and transiently transfected into HepG2 cells or into primary adult rat hypatocytes. Transfection experiments in combination with DNase I footprinting analysis in vitro led to the identification of two negative regulatory regions spanning nucleotides -1,230 to -1,188 and -409 to -368 and designated (SIL1200) and (SIL400), respectively. When placed in front of the heterologous thymidine kinase promoter, SIL1200 and SIL400 reduced the activity of the chloramphenicol acetyl transferase reporter gene to 13% and 23% of the control value, respectively. No sex-dependent binding of liver nuclear extracts to the two silencers could be detected by in vitro footprinting or gel retardation assays. However, a sex-dependent footprint consistently stronger with male liver nuclear extracts than with female extracts was observed in the -320 to -294 region. A significant level of identity was found between the DNA sequence corresponding to this footprint and that of orphan steroid receptor elements as well as with that of a basal transcription element common to several CYP2C genes. However, the identity of a potential trans-acting factor binding between -320 and -294 or response of this element to growth hormone is as yet unknown. A sex- and GH secretory profile-dependent protein-DNA interaction in vitro was observed in the -107 to -95 region. In spite of the sequence similarity that exists between this region and the consensus binding site for HNF-1, this region does not bind HNF-1 alpha. This element acted as a repressor on the heterologous thymidine kinase promoter. To date, the two silencer elements and possibly also the HNF-1-like element are the only functional elements defined in the CYP2C11 gene, and it is conceivable that induction of the gene involves derepression of the silencer elements.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:geneSymbol
CYP2C11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
805-19
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8068205-Animals, pubmed-meshheading:8068205-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:8068205-Base Sequence, pubmed-meshheading:8068205-Binding Sites, pubmed-meshheading:8068205-Cells, Cultured, pubmed-meshheading:8068205-Cloning, Molecular, pubmed-meshheading:8068205-Cytochrome P-450 Enzyme System, pubmed-meshheading:8068205-DNA, pubmed-meshheading:8068205-DNA-Binding Proteins, pubmed-meshheading:8068205-Female, pubmed-meshheading:8068205-Genes, Reporter, pubmed-meshheading:8068205-Growth Hormone, pubmed-meshheading:8068205-Liver, pubmed-meshheading:8068205-Male, pubmed-meshheading:8068205-Molecular Sequence Data, pubmed-meshheading:8068205-Promoter Regions, Genetic, pubmed-meshheading:8068205-Rats, pubmed-meshheading:8068205-Rats, Sprague-Dawley, pubmed-meshheading:8068205-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:8068205-Sequence Homology, Nucleic Acid, pubmed-meshheading:8068205-Sex Factors, pubmed-meshheading:8068205-Steroid 16-alpha-Hydroxylase, pubmed-meshheading:8068205-Steroid Hydroxylases, pubmed-meshheading:8068205-Transcription, Genetic
pubmed:year
1994
pubmed:articleTitle
Characterization of the proximal promoter and two silencer elements in the CYP2C11 gene expressed in rat liver.
pubmed:affiliation
Department of Medical Nutrition, Huddinge University Hospital, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't