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

Dean, Greg, Young, David A., Edwards, Dylan R. and Clark, Ian M. (2000) The human tissue inhibitor of metalloproteinases (TIMP)-1 gene contains repressive elements within the promoter and intron 1. Journal of Biological Chemistry, 275 (42). pp. 32664-32671. ISSN 0021-9258

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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.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User:	Pure Connector
Date Deposited:	18 Dec 2013 13:22
Last Modified:	28 Mar 2025 05:46
URI:	https://ueaeprints.uea.ac.uk/id/eprint/47073
DOI:	10.1074/jbc.275.42.32664

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