Structure of the murine tissue factor gene. Chromosome location and conservation of regulatory elements in the promoter.
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.
Mackman
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N
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Imes
S
S
Maske
W H
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Taylor
B
B
Lusis
A J
AJ
Drake
T A
TA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D015342:DNA Probes; D005091:Exons; D005786:Gene Expression Regulation; D007438:Introns; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013925:Thromboplastin / Q000737:chemistry / Q000235:genetics*
D015342:DNA Probes; D004247:DNA; D013925:Thromboplastin