Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-4
pubmed:dateCreated
1992-2-4
pubmed:abstractText
The transcriptional mechanisms which contribute to the regulation of nerve growth factor (NGF) production are still largely unknown. We previously expressed the NGF promoter region in transgenic mice to localize cis regulatory elements to within 5 kb of the promoter. To further map these elements, and to begin to study the corresponding transacting factors, we here assayed the effects of 5' deletions and point mutations and examined the binding of nuclear factors to the NGF promoter region using L929 cell fibroblasts. Sequential deletions delineated regions upstream from the promoter which stimulated and inhibited transcription. DNAse-1 footprinting experiments identified four upstream segments, designated F2, F4, F6 and F8, which bound L929 cell nuclear proteins. F2 and F4 mapped to stimulatory and F6 and F8 to inhibitory regions. Competition experiments using a heptanucleotide present in both F2 and F4 segments suggested that they may be bound by related factors. Gel shift assays showed that the F8 binding proteins are less abundant in L929 cells than in NIH 3T3 fibroblasts and B16 melanoma cells. In addition to the upstream segments, a downstream AP-1 consensus sequence bound L929 nuclear proteins. Mutation of the AP-1 consensus sequence eliminated binding of nuclear proteins and reduced transcriptional activity. Our results indicate that transcriptional activator as well as suppressor regions surround the NGF gene promoter. The regulation of NGF production is likely to involve cis elements within these regions and transacting factors that bind to them.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-64
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:1661823-Animals, pubmed-meshheading:1661823-Base Sequence, pubmed-meshheading:1661823-Chromosome Deletion, pubmed-meshheading:1661823-Deoxyribonuclease I, pubmed-meshheading:1661823-Growth Hormone, pubmed-meshheading:1661823-Humans, pubmed-meshheading:1661823-L Cells (Cell Line), pubmed-meshheading:1661823-Mice, pubmed-meshheading:1661823-Molecular Sequence Data, pubmed-meshheading:1661823-Mutagenesis, Site-Directed, pubmed-meshheading:1661823-Nerve Growth Factors, pubmed-meshheading:1661823-Oligodeoxyribonucleotides, pubmed-meshheading:1661823-Oligonucleotide Probes, pubmed-meshheading:1661823-Promoter Regions, Genetic, pubmed-meshheading:1661823-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:1661823-Restriction Mapping, pubmed-meshheading:1661823-Transcription, Genetic, pubmed-meshheading:1661823-Transfection
pubmed:year
1991
pubmed:articleTitle
Structural and functional identification of regulatory regions and cis elements surrounding the nerve growth factor gene promoter.
pubmed:affiliation
Evans Department of Clinical Research, University Hospital, Boston, MA 02118.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't