[en] The human MAGE1 gene directs the expression of an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. MAGE1 belongs to a family of genes that are expressed in a number of tumors of various histological types but not in normal tissues except testis. The MAGE genes are arranged in two groups that are located within two different regions of the human X chromosome (Xq26-qter and Xp21.3). By hybridizing mouse genomic libraries with a MAGE1 probe, we identified three homologous genes. Two of these mouse genes, Smage1 and Smage2, are more than 99% identical to each other and encode the same protein of 330 aa. The 5' noncoding region of Smage2 provides the potential for regulating the expression of the gene through several different promoters located in front of alternative first exons. The third gene, Smage3, has the structure of a processed transcript. It codes for a protein with only 11 aa substitutions with respect to the Smage1/2 product. Somatic cell hybrids and interspecific backcross analysis showed that Smage3 is autosomal and that Smage1 and Smage2 are located between the Dmd and the Ar loci on the mouse X chromosome. Since this region is syntenic to the human Xp21.1-p22.1 region, we conclude that Smage1 and Smage2 are homologous to the MAGE-Xp rather than to the MAGE-Xq genes. Smage1/2 transcripts were detected in several tumor and embryonal cell lines but not in normal mouse tissues with the exception of testis. Expression of Smage3 was found in embryos from Day 11 to Day 15.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
De Backer, O.
Verheyden, A. M.
Martin, B.
Godelaine, D.
De Plaen, E.
Brasseur, Robert ; Université de Liège - ULiège > Gembloux Agro-Bio Tech
Avner, P.
Boon, T.
Language :
English
Title :
Structure, chromosomal location, and expression pattern of three mouse genes homologous to the human MAGE genes.
Amar, L. C., Arnaud, D., Cambrou, J., Guenet, J. L., and Avner, P. R. (1985). Mapping of the mouse X chromosome using random genomic probes and an interspecific mouse cross. EMBO J. 4: 3695-3700.
Arnaud, D., Mattei, M. G., and Avner, P. (1993). A panel of deleted mouse X chromosome somatic cell hybrids derived from the embryonic stem cell line HD3 show preferential breakage in the Hprt-DXHX254E region. Genomics 18: 520-526.
Avner, P., Amar, L., Dandolo, L., and Guenet, J. L. (1988). Genetic analysis of the mouse using interspecific crosses. Trends Genet. 4: 18-23.
Avner, P., Arnaud, D., Amar, L. C., Cambrou, J. C., Winking, H., and Russell, L. B. (1987). Characterisation of a panel of somatic cell hybrids for the regional mapping of the mouse X chromosome. Proc. Natl. Acad. Sci. USA 84: 5330-5334.
Bardoni, B., Zanaria, E., Guioli, S., Floridia, G., Worley, K. C., Tonini, G., Ferrante, E., Chiumello, G., Mc Cabe, E. R. B., Fraccaro, M., Zuffardi, O., and Caminero, G. (1994). A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nature Genet. 7: 497-501.
Beachy, P. A., Krasnow, M. A., Gavis, E. R., and Hogness, D. S. (1988). An Ultrabithorax protein binds sequences near its own and the Antennapedia PI promoters. Cell 55: 1069-1081.
Brasseur, R. (1991). Differentiation of lipid-associating helices by use of three-dimensional molecular hydrophobicity potential calculations. J. Biol. Chem. 266: 16120-16127.
Capecchi, M. R. (1989). Altering the genome by homologous recombination. Science 244: 1288-1292.
Cattanach, B. M., Rasberry, C., Evans, E. P., Dandolo, L., Simmler, M. C., and Avner, P. (1991). Genetic and molecular evidence of an X-chromosome deletion spanning the tabby (Ta) and testicular feminization (Tfm) loci in the mouse. Cytogenet. Cell Genet. 56: 137-143.
Chomez, P., De Plaen, E., Van Pel, E., De Smet, C., Szikora, J.-P., Lurquin, C., Lebacq-Verheyden, A.-M., and Boon, T. (1992). Efficient expression of turn" antigen P91A by transfected subgenic fragments. Immunogenetics 35: 241-252.
Cox, D. R., and Epstein, J. (1985). Comparative gene mapping of human chromosome 21 and mouse chromosome 16. Ann. N.Y. Acad. Sci. 450: 169-177.
Davis, L. G., Dibner, M. D., and Battey, J. F. (1986). Basic Methods in Molecular Biology pp. 130-146, Elsevier, New York.
De Plaen, E., Arden, K., Traversari, C., Gaforio, J. J., Szikora, J.-P., De Smet, C., Brasseur, F., van der Bruggen, P., Lethe, B., Lurquin, C., Brasseur, R., Chomez, P., De Backer, O., Cavenee, W., and Boon, T. (1994). Structure, chromosomal localization and expression of twelve genes of the MAGE family. Immunogenetics 40:360-369.
De Plaen, E., Lurquin, C., Van Pel, A., Mariame, B., Szikora, J.-P., Wolfel, T., Sibille, C., Chomez, P., and Boon, T. (1988). Immunogenic (turn) variants of mouse tumor P815: Cloning of the gene of turnantigen P91A and identification of the turnmutation. Proc. Natl. Acad. Sci. USA 85: 2274-2278.
Emerson, C. P. J. (1993). Embryonic signals for skeletal myogenesis: Arriving at the beginning. Curr. Opin. Cell Biol. 5: 1057-1064.
Feinberg, A. P., and Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132: 6-13.
Frohman, M. A., Dush, M., and Martin, G. (1988). Rapid amplification of full-length c DNAfrom rare transcripts: Amplification using a single gene-specific oligonucleotide primer. Proc. Natl. Acad. Sci. USA 85: 8998.
Gaboriaud, C., Bissery, V., Benchetrit, T., and Mornon, J. P. (1987). Hydrophobic cluster analysis: An efficient new way to compare and analyse amino acid sequences. FEBS Lett. 224: 149-155.
Herman, G. E., Berry, M., Munro, E., Craig, I. W., and Levy, E. R. (1991). The construction of human somatic cell hybrids containing portions of the mouse X chromosome and their use to generate DNA probes via interspersed repetitive sequence polymerase chain reaction. Genomics 10: 961-970.
Kozak, M. (1992). Regulation of translation in eukaryotic systems. Annu. Rev. Cell Biol. 8: 197-225.
Kyte, J., and Doolittle, R. F. (1982). A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157:105-132.
Lurquin, C., Van Pel, A., Mariame, B., De Plaen, E., Szikora, J.-P., Janssens, C., Reddehase, M., Lejeune, J., and Boon, T. (1989). Structure of the gene coding for turn transplantation antigen P91A: A peptide encoded by the mutated exon is recognized with Ld by cytolytic T cells. Cell 58: 293-303.
Mar, J. H., and Ordahl, C. P. (1990). M-CAT binding factor, a novel trans-acting factor governing muscle-specific transcription. Mol. Cell. Biol. 10:4271-4283.
Marth, J. D., Overell, R. W., Meier, K. E., Krebs, E. G., and Perlmutter, R. M. (1988). Translational activation of the lek proto-onco-gene. Nature 332: 171-173.
Maruyama, K., Usami, M., Aizawa, T., and Yoshikawa, K. (1991). A novel brain-specific m RNA encoding nuclear protein (necdin) expressed in neurally differentiated embryonal carcinoma cells. Biochem. Biophys. Res. Commun. 178: 291-296.
Muscatelli, F., Walker, A. P., De Plaen, E., Stafford, A. N., and Monaco, A. P. (1995). Isolation and characterisation of a new MAGE gene family in the Xp21.3 region. Proc. Natl. Acad. Sci. USA, in press.
Pribyl, T. M., and Martinson, H. G. (1988). Transcription termination at the chicken beta H-globin gene. Mol. Cell. Biol. 8: 5369-5377.
Scholer, H. R. (1991). Octamania: The Pou factors in murine development. Trends Genet. 7: 323-329.
Suzuki, N., Rohdewohld, H., Neuman, T., Gruss, P., and Scholer, H. R. (1990). Oct-6: A POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J. 9: 3723-3732.
van der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., Van den Eynde, B., Knuth, A., and Boon, T. (1991). A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643-1647.
