Linked Life Data

7499234

Source:http://linkedlifedata.com/resource/pubmed/id/7499234

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
1996-1-17
pubmed:abstractText
The platelet-derived growth factor (PDGF) A-chain has been implicated in the initiation and progression of vascular occlusive lesions. The elements in the human PDGF-A promoter that mediate increased expression of the gene in vascular endothelial cells have not been identified. A potent inducer of PDGF-A expression in endothelial cells is phorbol 12-myristate 13-acetate (PMA). 5'-Deletion and transfection analysis revealed that a G+C-rich region in the proximal PDGF-A promoter is required for PMA-inducible gene expression. This region bears overlapping consensus recognition sequences for Sp1 and Egr-1. PMA induces Egr-1 mRNA expression within 1 h, whereas PDGF-A transcript levels increase after 2-4 h. Constitutive levels of Sp1 are not altered over 24 h. A specific nucleoprotein complex is formed when an oligonucleotide bearing the G+C-rich element is incubated with nuclear extracts from PMA-treated cells. The temporal appearance of this complex is consistent with the transient increase in Egr-1 transcripts. Antibodies to Egr-1 completely supershift the PMA-induced complex. Interestingly, increased nuclear levels of Egr-1 attenuate the ability of Sp1 to interact with the oligonucleotide, implicating competition between Egr-1 and Sp1 for the G+C-rich element. Binding studies with recombinant proteins demonstrate that Egr-1 can displace Sp1 from this region. Insertion of the G+C-rich element into a hybrid promoter-reporter construct confers PMA inducibility on the construct. Mutations that abolish Egr-1 binding also abrogate expression induced by PMA or overexpressed Egr-1. These findings demonstrate that PMA-induced Egr-1 displaces Sp1 from the G+C-rich element and activates expression driven by the PDGF-A proximal promoter in endothelial cells. The Sp1/Egr-1 displacement mechanism may be an important regulatory circuit in the control of inducible gene expression in vascular endothelial cells.
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
17
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27679-86
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7499234-Animals, pubmed-meshheading:7499234-Aorta, pubmed-meshheading:7499234-Base Sequence, pubmed-meshheading:7499234-Binding Sites, pubmed-meshheading:7499234-Cattle, pubmed-meshheading:7499234-Cell Nucleus, pubmed-meshheading:7499234-Cells, Cultured, pubmed-meshheading:7499234-Consensus Sequence, pubmed-meshheading:7499234-DNA-Binding Proteins, pubmed-meshheading:7499234-Early Growth Response Protein 1, pubmed-meshheading:7499234-Endothelium, Vascular, pubmed-meshheading:7499234-Gene Expression, pubmed-meshheading:7499234-Humans, pubmed-meshheading:7499234-Immediate-Early Proteins, pubmed-meshheading:7499234-Models, Biological, pubmed-meshheading:7499234-Molecular Sequence Data, pubmed-meshheading:7499234-Platelet-Derived Growth Factor, pubmed-meshheading:7499234-Promoter Regions, Genetic, pubmed-meshheading:7499234-RNA, Messenger, pubmed-meshheading:7499234-Sp1 Transcription Factor, pubmed-meshheading:7499234-Tetradecanoylphorbol Acetate, pubmed-meshheading:7499234-Transcription, Genetic, pubmed-meshheading:7499234-Transcription Factors, pubmed-meshheading:7499234-Zinc Fingers
pubmed:year
1995
pubmed:articleTitle
Interplay of Sp1 and Egr-1 in the proximal platelet-derived growth factor A-chain promoter in cultured vascular endothelial cells.
pubmed:affiliation
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't