Nucleotide Sequence of the Gene Encoding Murine Tissue Factor Pathway Inhibitor-2

Summary

Tissue factor pathway inhibitor-2 (TFPI-2), also known as placental protein 5, is a 32 kDa extracellular matrix-associated serine proteinase inhibitor consisting of three tandemly-arranged Kunitz-type domains. Two overlapping genomic clones containing sequences encoding murine TFPI-2 were isolated from a A FIXII 129 SVJ mouse genomic library, and the complete nucleotide sequence of the gene was determined. The murine TFPI-2 gene spans approximately 9.3 kilobases and consists of five exons and four introns. The nucleotide sequences surrounding all the exon-intron boundaries are highly conserved and obey the GT-AG rule. Each Kunitz-type domain is encoded by a single exon, similar to that observed for other Kunitz-type proteinase inhibitors. A total of 1,577 bp of the 3’-flanking region contains a probable polyadenylation site (ATTAAA) at +5,759 and an apparent cleavage or termination site (CATTG) at +6,170. The 5’-flanking region of the murine TFPI-2 gene contains a prototypical TATA box, a GC box and two CAAT boxes. In addition, several candidate transcription factor binding sites responsible for placenta-, endothelial cell-, and smooth muscle cell-specific expression of the TFPI-2 gene were also identified.

Keywords

Tissue factor pathway inhibitor-2 - Kunitz-type proteinase inhibitor - gene - mouse

• References

• 1 Sprecher CA, Kisiel W, Mathewes S, Foster DC. Molecular cloning, expression, and partial characterization of a second human tissue-factorpathway inhibitor. Proc Natl Acad Sci USA 1994; 91: 3353-7.
• 2 Bützow R, Huhtala M-L, Bohn H, Virtanen I. Seppälä Purification and characterization of placental protein 5. Biochem Biophys Res Commun 1988; 150: 483-90.
• 3 Miyagi Y, Yasumitsu H, Eki T, Miyata S, Koshikawa N, Hirahara F, Aoki I, Misugi K, Miyazaki K. Assignment of the human PP5/TFPI-2 gene to 7q22 by FISH and PCR-based human/rodent cell hybrid mapping panel analysis. Genomics 1996; 35: 267-8.
• 4 Petersen LC, Sprecher CA, Foster DC, Blumberg H, Hamamoto T, Kisiel W. Inhibitory properties of a novel human Kunitz-type protease inhibitor homologous to tissue factor pathway inhibitor. Biochemistry 1996; 35: 266-72.
• 5 Kamei S, Petersen LC, Sprecher CA, Foster DC, Kisiel W. Inhibitory properties of human recombinant Arg²⁴ →Gln Type-2 tissue factor pathway inhibitor (R24Q TFPI-2). Thromb Res 1999; 94: 147-52.
• 6 Rao CN, Gomez DE, Woodley DT, Thorgeirsson UP. Partial characterization of novel serine proteinase inhibitors from human umbilical vein endothelial cells. Arch Biochem Biophys 1995; 319: 55-62.
• 7 Kamei S, Arepally G, Foster DC, Kisiel W. unpublished results
• 8 Rao CN, Liu YY, Peavey CL, Woodley DT. Novel extracellular matrixassociated serine proteinase inhibitors from human skin fibroblasts. Arch Biochem Biophys 1995; 317: 311-4.
• 9 Rao CN, Peavey CL, Liu YY, Lapiere JC, Woodley DT. Partial characterization of matrix-associated serine protease inhibitors from human skin cells. J Invest Dermatol 1995; 104: 379-83.
• 10 Udagawa K, Miyagi Y, Hirahara F, Miyagi E, Nagashima Y, Minaguchi H, Misugi K, Yasumitsu H, Miyazaki K. Specific expression of PP5/TFPI-2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization. Placenta 1998; 19: 217-23.
• 11 Iino M, Foster DC, Kisiel W. Quantification and characterization of human endothelial cell-derived tissue factor pathway inhibitor-2. Arterioscler Thromb Vasc Biol 1998; 18: 40-6.
• 12 Rao CN, Cook B, Liu Y, Chilukuri K, Stack MS, Foster DC, Kisiel W, Woodley DT. HT-1080 fibrosarcoma cell matrix degradation and invasion are inhibited by the matrix-associated serine protease inhibitor TFPI-2/33kDa MSPI. Int J Cancer 1998; 76: 749-56.
• 13 Rao CN, Mohanam S, Puppala A, Rao JS. Regulation of ProMMP-1 and ProMMP-3 activation by tissue factor pathway inhibitor-2/matrix-associated serine protease inhibitor. Biochem Biophys Res Commun 1999; 255: 94-8.
• 14 Shinoda E, Yui Y, Hattori R, Tanaka M, Inoue R, Aoyama T, Takimoto Y, Mitsui Y, Miyahara K, Shizuta Y, Sasayama S. Tissue factor pathway inhibitor-2 is a novel mitogen for vascular smooth muscle cells. J Biol Chem 1999; 274: 5379-84.
• 15 Gubler U, Hoffman BJ. A simple and very efficient method for generating cDNA libraries. Gene 1983; 25: 263-9.
• 16 Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988; 239: 487-91.
• 17 Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K. eds. Current protocols in molecular biology. 1994-1998. John Wiley &: Sons,Inc.;
• 18 Frohman MA, Dush MK, Martin GR. Rapid production of full-length cDNAs from rare transcripts: Amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci USA 1988; 85: 8998-9002.
• 19 Mount SM. A catalogue of splice junction sequences. Nucleic Acids Res 1982; 10: 459-72.
• 20 Sharp PA. Speculations on RNA splicing. Cell 1981; 23: 643-6.
• 21 Miyagi Y, Yasumitsu H, Mizushima H, Koshikawa N, Matsuda Y, Itoh H, Hori T, Aoki I, Misugi K, Miyazaki K. Cloning of the cDNA encoding mouse PP5/TFPI-2 and mapping of the gene to chromosome 6. DNA Cell Biology 1996; 15: 947-54.
• 22 Van der Logt CPE, Reitsma PH, Bertina RM. Intron-exon organization of the human gene coding for the lipoprotein-associated coagulation inhibitor: The factor Xa dependent inhibitor of the extrinsic pathway of coagulation. Biochemistry 1991; 30: 1571-7.
• 23 Girard TJ, Eddy R, Wesselschmidt RL, MacPhail LA, Likert KM, Byers MG, Shows TB, Broze Jr GJ. Structure of the human lipoprotein-associated coagulation inhibitor gene. Intron/exon gene organization and localization of the gene to chromosome 2. J Biol Chem 1991; 266: 5036-41.
• 24 Vetr H, Kögler M, Gebhard W. The domain structure of the inhibitor subunit of human inter-α-trypsin inhibitor reflects the exon structure of its gene. FEBS Lett 1989; 245: 137-40.
• 25 Ponte P, Gonzalez-DeWhitt P, Schilling J, Miller J, Hsu D, Greenberg B, Davis K, Wallace W, Lieberburg I, Fuller F, Cordell B. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 1988; 331: 525-7.
• 26 Bucher P. Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequences. J Mol Biol 1990; 212: 563-78.
• 27 Faisst S, Meyer S. Compilation of vertebrate-encoded transcription factors. Nucleic Acids Res 1992; 20: 3-26.
• 28 Miyagi Y, Koshikawa N, Yasumitsu H, Miyagi E, Hirahara F, Aoki I, Misugi K, Umeda M, Miyazaki K. cDNA cloning and mRNA expression of a serine proteinase inhibitor secreted by cancer cells: Identification as placental protein 5 and tissue factor pathway inhibitor-2. J Biochem (Tokyo) 1994; 116: 939-42.
• 29 Steger DJ, Hecht JH, Mellon PL. GATA-binding proteins regulate the human gonadotropin α-subunit gene in the placenta and pituitary gland. Mol Cell Biol 1994; 14: 5592-602.
• 30 Delegeane AM, Ferland LH, Mellon PL. Tissue-specific enhancer of the human glycoprotein hormone α-subunit gene: Dependence on cyclic AMPinducible elements. Mol Cell Biol 1987; 07: 3994-4002.
• 31 Steger DJ, Altschmied J, Buscher M, Mellon PL. Evolution of placentaspecific gene expression: Comparison of the equine human gonadotropin alpha-subunit genes. Mol Endocrinol 1991; 05: 243-55.
• 32 Ng Y-K, George KM, Engel JD, Linzer DIH. GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene. Development 1994; 120: 3257-66.
• 33 Yamada K, Harada N, Honda S, Takagi Y. Regulation of placenta-specific expression of the aromatase cytochrome P-450 gene. Involvement of the trophoblast-specific element binding protein. J Biol Chem 1995; 270: 25064-9.
• 34 Bi S, Gavrilova O, Gong D-W, Mason MM, Reitman M. Identification of aplacental enhancer for the human leptin gene. J Biol Chem 1997; 272: 30583-8.
• 35 Wang Z, Melmed S. Functional map of a placenta-specific enhancer of the human leukemia inhibitory factor receptor gene. J Biol Chem 1998; 273: 26069-77.
• 36 Jiang S-W, Trujillo MA, Eberhardt NL. Human chorionic somatomammotropin enhancer function is mediated by cooperative binding of TEF-1 and CSEF-1 to multiple, low-affinity binding sites. Mol Endocrinol 1997; 11: 1223-32.
• 37 Jameson JL, Hollenberg AN. Regulation of chorionic gonadotropin gene expression. Endocr Rev 1993; 14: 203-21.
• 38 Mackman N. Regulation of the tissue factor gene. FASEB J 1995; 09: 883-9.
• 39 Lakshminarayanan V, Drab-Weiss EA, Roebuck KA. H2O2 and tumor necrosis factor-α induce differential binding of the redox-responsive transcription factors AP-1 and NF-kB to the interleukin-8 promoter in endothelial and epithelial cells. J Biol Chem 1988; 273: 32670-8.
• 40 Cowan PJ, Tsang D, Pedic CM, Abbott LR, Shinkel TA, d’Apice AJF, Pearse MJ. The human ICAM-2 promoter is endothelial cell-specific in vitro and in vivo and contains critical Sp1 and GATA binding sites. J Biol Chem 1998; 273: 11737-44.
• 41 Fadel BM, Boutet SC, Quertermous T. Octamer-dependent in vivo expression of the endothelial cell-specific TIE2 gene. J Biol Chem 1999; 274: 20376-83.
• 42 Gille J, Swerlick RA, Caughman SW. Transforming growth factor-α-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding transactivation. EMBO J 1997; 16: 750-9.
• 43 Hata Y, Duh E, Zhang K, Robinson GS, Aiello LP. Transcriptional factors Sp1 and Sp3 alter vascular endothelial growth facctor receptor expression through a novel recognition sequence. J Biol Chem 1998; 273: 19294-303.
• 44 Treisman R. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell 1986; 46: 567-74.
• 45 Shimizu RT, Blank RS, Jervis R, Lawrenz-Smith SC, Owens GK. The smooth muscle α-actin gene promoter is differentially regulated in smooth muscle versus non-smooth muscle cells. J Biol Chem 1995; 270: 7631-43.
• 46 Ernst H, Walsh K, Harrison CA, Rosenthal N. The myosin light chain enhancer and the skeletal actin promoter share a binding site for factors involved in muscle-specific gene expression. Mol Cell Biol 1991; 11: 3735-44.
• 47 Bützow R, Alfthan H, Stenman UH, Suikkari AM, Bohn H, Seppälä M. Immunofluorometric demonstration and quantification of placental protein 5 in the absence of pregnancy. Clin Chem 1988; 34: 1591-3.