Linked Life Data

9182725

Source:http://linkedlifedata.com/resource/pubmed/id/9182725

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-7-8
pubmed:databankReference
pubmed:abstractText
The active forms of all of the matrix metalloproteinases (MMPs) are inhibited by a family of specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Inhibition represents a major level of control of MMP activity. A detailed knowledge of the mechanisms controlling TIMP gene expression is therefore important. We have isolated a genomic clone of the human TIMP-1 gene. A 3 kbp XbaI fragment has been sequenced; this fragment contains 1718 bp 5' flanking sequences, exon 1, a 929 bp intron 1 and part of exon 2. Computer analysis reveals 10 consensus sequences for Sp1, six for activating protein 1 (AP-1), six for polyoma enhancer A3 (PEA3), 12 for AP-2 and five CCAAT boxes. The region hybridizing with a murine TIMP-1 promoter fragment has been subcloned and analysed further. RNase protection identifies six transcription start points, making exon 1 up to 48 bp in length. Transient transfection of promoter-chloramphenicol O-acetyltransferase reporter constructs into primary human connective tissue fibroblasts shows that a 904 bp fragment that hybridizes to a murine TIMP-1 promoter fragment contains a functional promoter. Constructs of -738/+95 to -194/+21 are inducible with serum or phorbol ester to a similar extent to the endogenous TIMP-1 gene. These results and further mapping with 5' deletion mutants from the -738/+95 region have demonstrated that an AP-1 site at -92/-86 is essential for basal expression of the gene. Point mutations within this region have further confirmed the role of this site, along with a more minor role for a neighbouring PEA3 site, in basal expression. Deletions from the 3' end also implicate a region across the exon 1/intron 1 boundary and especially +21 to +58 in basal expression. The +21/+58 region contains a putative binding site for the transcription factor leader-binding protein 1 (LBP-1). Gel-shift analysis shows that protein binds specifically to this region, but competition studies suggest that it is unlikely to be LBP-1.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-1420363, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-1445287, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-1634117, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-1661164, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-1849903, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-2120112, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-2166509, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-271968, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-2820711, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-2850484, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-3037497, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-3670292, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-4291934, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-6828386, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-7487894, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8053949, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8093070, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8112602, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8114710, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8195127, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8309995, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8408003, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8515078, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8557686, http://linkedlifedata.com/resource/pubmed/commentcorrection/9182725-8559663
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0264-6021
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
324 ( Pt 2)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
611-7
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:9182725-Animals, pubmed-meshheading:9182725-Base Sequence, pubmed-meshheading:9182725-Binding Sites, pubmed-meshheading:9182725-Cells, Cultured, pubmed-meshheading:9182725-Cloning, Molecular, pubmed-meshheading:9182725-Consensus Sequence, pubmed-meshheading:9182725-DNA-Binding Proteins, pubmed-meshheading:9182725-Exons, pubmed-meshheading:9182725-Fibroblasts, pubmed-meshheading:9182725-Gene Expression Regulation, pubmed-meshheading:9182725-Gene Library, pubmed-meshheading:9182725-Glycoproteins, pubmed-meshheading:9182725-Humans, pubmed-meshheading:9182725-Introns, pubmed-meshheading:9182725-Mice, pubmed-meshheading:9182725-Molecular Sequence Data, pubmed-meshheading:9182725-Point Mutation, pubmed-meshheading:9182725-Promoter Regions, Genetic, pubmed-meshheading:9182725-Recombinant Fusion Proteins, pubmed-meshheading:9182725-Tissue Inhibitor of Metalloproteinases, pubmed-meshheading:9182725-Transcription, Genetic, pubmed-meshheading:9182725-Transcription Factor AP-1, pubmed-meshheading:9182725-Transcription Factors, pubmed-meshheading:9182725-Transfection
pubmed:year
1997
pubmed:articleTitle
Transcriptional activity of the human tissue inhibitor of metalloproteinases 1 (TIMP-1) gene in fibroblasts involves elements in the promoter, exon 1 and intron 1.
pubmed:affiliation
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, U.K.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't