Faculty Research 1990 - 1999

Title

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

Document Type

Article

Publication Date

1992

Keywords

Animal, Base-Sequence, Chromosome-Mapping, DNA, DNA-Probes, Exons, Gene-Expression-Regulation, Introns, Mice, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Molecular-Sequence-Data, Polymorphism-Restriction-Fragment-Length, Promoter-Regions-(Genetics), Regulatory-Sequences-Nucleic-Acid, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Thromboplastin: ge

JAX Source

Arterioscler Thromb 1992 Apr;12(4):474-83

Grant

HL16411/HL/NHLBI, HL30568/HL/NHLBI, HL42488/HL/NHLBI

Abstract

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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