A sequence-selective single-strand DNA-binding protein regulates basal transcription of the murine tissue inhibitor of metalloproteinases-1 (Timp-1) Gene

Phillips, Blaine W., Sharma, Renuka, Leco, Pamela A. and Edwards, Dylan R. ORCID: https://orcid.org/0000-0002-3292-2064 (1999) A sequence-selective single-strand DNA-binding protein regulates basal transcription of the murine tissue inhibitor of metalloproteinases-1 (Timp-1) Gene. Journal of Biological Chemistry, 274 (32). pp. 22197-22207. ISSN 0021-9258

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Abstract

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is important in maintaining the extracellular proteolytic balance during tissue remodeling processes. To allow homeostatic tissue turnover, the murine Timp-1 gene is expressed by most cells at a low basal level, and during acute remodeling its transcription is activated by a variety of stimuli. A non-consensus AP-1-binding site (5′-TGAGTAA-3′) that is conserved in mammalian timp-1 genes is a critical element in basal and serum-stimulated transcription. We show here that each strand of this unusual AP-1 site binds a distinct single-stranded DNA-binding protein, although neither strand from a perfect consensus AP-1 site from the human collagenase gene shows similar binding. One of the single-strand binding factors, which we term ssT1, binds to a second upstream Timp-1 region between nucleotides −115 and −100. Deletion analysis demonstrated that this region is important in basal but not serum-inducible transcription. The ssT1 factor was 52–54 kDa by UV cross-linking of electrophoretic mobility shift assays and Southwestern blot analysis. Its binding to DNA shows sequence selectivity rather than specificity, with 5′-CT/ATTN(4–6)ATC-3′ as a favored motif. Multiple ssT1-like activities were found in nuclear extracts from mouse fibroblasts and rat liver and testis, suggesting that these factors may regulate basal Timp-1 transcription in a tissue-specific fashion.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Science > Research Groups > Cells and Tissues
Depositing User:	Pure Connector
Date Deposited:	01 Apr 2014 12:38
Last Modified:	04 Mar 2024 16:53
URI:	https://ueaeprints.uea.ac.uk/id/eprint/48317
DOI:	10.1074/jbc.274.32.22197

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