Hammani, K
Blakis, A
Morsette, D
Bowcock, A M
Schmutte, C
Henriet, Patrick
[UCL]
DeClerck, Y A
We report here the characterization of the human tissue inhibitor of metalloproteinases-2 (TIMP-2) gene. The gene is 83 kilobase pairs (kb) long with exon-intron splicing sites located in preserved positions among the three members of the TIMP family. A 2.6-kb genomic DNA fragment flanking the 5'-end of the gene contains several regulatory elements including five Sp1, two AP-2, one AP-1, and three PEA-3 binding sites. Despite the presence of a complete AP-1 consensus at position -281, the promoter did not respond to 12-O-tetradecanoylphorbol-13-acetate treatment. However, 12-O-tetradecanoylphorbol-13-acetate response was generated by insertion of a similar AP-1 consensus at position -71, indicating the importance of the positioning of this motif. The promoter contains a typical CpG island; however, methylation of this island did not seem to influence gene expression. Analysis of the 3'-end of the gene revealed that the two mRNAs for TIMP-2 (1.2 and 3.8 kb) differ by the selection of their polyadenylation signal sites, but selection of these sites does not affect RNA stability. In summary, the TIMP-2 gene has several features observed in housekeeping genes, and differs significantly from TIMP-1 and TIMP-3 genes. These differences are likely to explain the specific roles that these inhibitors play in the regulation of matrix metalloproteinases.
Bibliographic reference |
Hammani, K ; Blakis, A ; Morsette, D ; Bowcock, A M ; Schmutte, C ; et. al. Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene.. In: The Journal of biological chemistry, Vol. 271, no.41, p. 25498-505 (1996) |
Permanent URL |
http://hdl.handle.net/2078.1/132188 |