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The human tissue inhibitor of metalloproteinases (TIMP)-1 gene contains repressive elements within the promoter and intron 1

Lookup NU author(s): Professor David YoungORCiD

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Abstract

Expression of the TIMP-1 (tissue inhibitor of metalloproteinases-1) gene is tightly controlled during embryonic development and in the adult animal. Previous studies have focused on elements within the gene promoter which activate transcription of the gene. Here, we identify two regions of the gene which repress transcription: An element upstream of the basal gene promoter at -1718/-1458, represses expression of a reporter gene by approximately 50%; addition of the first intron to any promoter-reporter construct also strongly represses gene expression. The TIMP-1 gene has a short first exon which is transcribed but not translated, with the translation start site located in exon 2. Deletion analysis through intron 1 reveals a number of potential regions which might mediate its effect. Protein binding studies and mutational analyses reveal that a repressive element at +684/+748 binds Sp1, Sp3, and an unidentified Ets-related factor to suppress transcription.

Publication metadata

Author(s): Dean G, Young DA, Edwards DR, Clark IM

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2000

Volume: 275

Issue: 42

Pages: 32664-71

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.275.42.32664

DOI: 10.1074/jbc.275.42.32664

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