Linked Life Data

8621730

Source:http://linkedlifedata.com/resource/pubmed/id/8621730

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1996-6-19
pubmed:abstractText
Previous studies have shown that transforming growth factor-beta (TGF-be ta) and tumor necrosis factor-alpha (TNF-alpha) modulate type I collagen gene expression in fibroblasts. To fine-map the corresponding response elements in the human alpha2(I) collagen (COL1A2) promoter, we have generated a series of 5' deletion promoter/chloramphenicol acetyltransferase (CAT) reporter gene constructs. Transient cell transfection assays using human dermal fibroblasts and stable transfection experiments using NIH 3T3 fibroblasts identified the region located between residues -265 and -241, as critical for TGF-beta response. Specifically, we demonstrate that this 25-base pair region mediates the up-regulatory effect of TGF-beta on COL1A2 promoter activity and allows antagonistic activity of TNF-alpha on the TGF-beta effect. Gel mobility shift assays indicate that nuclear factor binding to this 25-base pair region of COL1A2 promoter is competed by AP-1, but not NF-1 or NF-kappaB, oligonucleotides. Transient cell transfection experiments with plasmid constructs in which the potential AP-1-binding site located within this short region of promoter was modified by site-directed mutagenesis indicated that this element plays a significant role in the basal activity of the promoter. Furthermore, this sequence is essential for TGF-beta response and does not require the presence of the three Sp-1-binding sites located further upstream, between nucleotides -273 and -304. In addition, overexpression of c-jun in co-transfection experiments with COL1A2 promoter/CAT constructs blocks the TGF- beta response, further implicating AP-1 in the regulation of COL1A2 gene expression. Our results clarify the molecular mechanisms involved in the regulation of type I collagen gene expression and further emphasize the importance of AP-1 in mediating some of the TGF-beta effects on gene transcription.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3272-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8621730-Base Sequence, pubmed-meshheading:8621730-Binding Sites, pubmed-meshheading:8621730-Cells, Cultured, pubmed-meshheading:8621730-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:8621730-Collagen, pubmed-meshheading:8621730-DNA, pubmed-meshheading:8621730-DNA Primers, pubmed-meshheading:8621730-Fibroblasts, pubmed-meshheading:8621730-Gene Expression Regulation, pubmed-meshheading:8621730-Humans, pubmed-meshheading:8621730-Infant, Newborn, pubmed-meshheading:8621730-Male, pubmed-meshheading:8621730-Molecular Sequence Data, pubmed-meshheading:8621730-Mutagenesis, Site-Directed, pubmed-meshheading:8621730-Nuclear Proteins, pubmed-meshheading:8621730-Point Mutation, pubmed-meshheading:8621730-Polymerase Chain Reaction, pubmed-meshheading:8621730-Promoter Regions, Genetic, pubmed-meshheading:8621730-Recombinant Proteins, pubmed-meshheading:8621730-Skin, pubmed-meshheading:8621730-Transcription, Genetic, pubmed-meshheading:8621730-Transcription Factor AP-1, pubmed-meshheading:8621730-Transfection, pubmed-meshheading:8621730-Transforming Growth Factor beta, pubmed-meshheading:8621730-Tumor Necrosis Factor-alpha
pubmed:year
1996
pubmed:articleTitle
An AP-1 binding sequence is essential for regulation of the human alpha2(I) collagen (COL1A2) promoter activity by transforming growth factor-beta.
pubmed:affiliation
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't