Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene.
(1996) Journal of Biological Chemistry — Vol. 271, n° 41, p. 25498-25505 (1996)
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- Abstract
- 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.
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Hammani, K., Blakis, A., Morsette, D., Bowcock, A. M., Schmutte, C., Henriet, P., & DeClerck, Y. A. (1996). Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene. Journal of Biological Chemistry, 271(41), 25498-25505. https://hdl.handle.net/2078.5/204253 (Original work published 1996)