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Publication : Structure of the murine tissue factor gene. Chromosome location and conservation of regulatory elements in the promoter.

First Author  Mackman N Year  1992
Journal  Arterioscler Thromb Volume  12
Issue  4 Pages  474-83
PubMed ID  1348427 Mgi Jnum  J:1127
Mgi Id  MGI:49659 Doi  10.1161/01.atv.12.4.474
Citation  Mackman N, et al. (1992) Structure of the murine tissue factor gene. Chromosome location and conservation of regulatory elements in the promoter. Arterioscler Thromb 12(4):474-83
abstractText  Tissue factor (TF) is a transmembrane glycoprotein that mediates cellular initiation of the coagulation serine protease cascades. Moreover, expression of TF in human atherosclerotic plaques is likely to play a significant role in the thrombotic complications associated with plaque rupture. In this study the complete murine TF gene, Cf-3, was isolated from mouse NIH 3T3 cells and was found to consist of six exons spanning about 11 kilobase pairs (kbp) of DNA. A major transcriptional start site was located 24 bp downstream of a TATA box. Cf-3 was mapped to chromosome 3 by analysis of an intersubspecies test cross. Conserved transcription factor-binding sites were identified by comparison of 5' flanking regions of the murine and human TF genes. A region of the TF promoter required for constitutive expression exhibited 85% identity in DNA sequence and included two conserved binding sites for Sp1. Furthermore, two AP-1 sites and an NF-kappa B site were conserved in a 56-bp region necessary for transcriptional activation in response to bacterial lipopolysaccharide. These highly conserved regions of the TF promoter, which contain several binding sites for well-characterized transcription factors, are likely to be functionally important in the complex pattern of TF gene expression observed in a variety of cell types.
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