Promoter demethylation mediates the expression of ZNF645, a novel cancer/testis gene
Cancer/testis (CT) antigens exhibit highly tissue-restricted expression and are considered promising targets for cancer vaccines. Here we identified a novel CT gene ZNF645 which restrictively expresses in normal human testes and lung cancer patients (68.3%). To investigate the promoter methylation status of ZNF645, we carried out bisulfite genomic sequencing and found that the CpG island in its promoter was heavily methylated in normal lung tissues without the expression of ZNF645, whereas there was high demethylation in normal human testes and lung carcinoma tissues with its expression. Also ZNF645 could be remarkably activated in A549 and HEK293T cells treated by DNA demethylation agent 5'-aza-2'-deoxycytidine. And the dual luciferase assay revealed that the promoter activity of the ZNF645 was inhibited by methylation of the CpG island region. Therefore, we proposed that ZNF645 is a CT gene and activated in human testis and lung cancers by demethylation of its promoter region.
- Scanlan, M., Gure, A., Jungbluth, A., Old, L. and Chen, Y. (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 188, 22-32.
- Scanlan, M., Simpson, A. and Old, L. (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 4, 1.
- 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.
- Ross, M. and Grafham, D., et al. (2005) The DNA sequence of the human X chromosome. Nature 434, 325-337.
- Hofmann, O., Caballero, O., Stevenson, B., Chen, Y., Cohen, T., Chua, R., Maher, C., Panji, S., Schaefer, U., Kruger, A., Lehvaslaiho, M., Carninci, P., Hayashizaki, Y., Jongeneel, C., Simpson, A., Old, L. and Hide, W. (2008) Genome-wide analysis of cancer/testis gene expression. Proc. Natl. Acad. Sci. U.S.A. 105, 20422-20427.
- Tajima, K., Obata, Y., Tamaki, H., Yoshida, M., Chen, Y., Scanlan, M., Old, L., Kuwano, H., Takahashi, T. and Mitsudomi, T. (2003) Expression of cancer/testis (CT) antigens in lung cancer. Lung Cancer 42, 23-33.
- Bird, A. and Wolffe, A. (1999) Methylation-induced repression-belts, braces, and chromatin. Cell. 99, 451-454.
- Cedar, H. (1988) DNA methylation and gene activity. Cell. 53, 3-4.
- Bird, A. (2002) DNA methylation patterns and epigenetic memory. Genes. Dev. 16, 6-21.
- Simpson, A., Caballero, O., Jungbluth, A., Chen, Y. and Old, L. (2005) Cancer/testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 5, 615-625.
- De Smet, C., Lurquin, C., Lethe, B., Martelange, V. and Boon, T. (1999) DNA methylation is the primary silencing mechanism for a set of germ line- and tumor-specific genes with a CpG-rich promoter. Mol. Cell. Biol. 19, 7327-7335.
- Grunwald, C., Koslowski, M., Arsiray, T., Dhaene, K., Praet, M., Victor, A., Morresi-Hauf, A., Lindner, M., Passlick, B., Lehr, H., Schafer, S., Seitz, G., Huber, C., Sahin, U. and Tureci, O. (2006) Expression of multiple epigenetically regulated cancer/germline genes in nonsmall cell lung cancer. Int. J. Cancer 118, 2522-2528.
- Sigalotti, L., Fratta, E., Coral, S., Tanzarella, S., Danielli, R., Colizzi, F., Fonsatti, E., Traversari, C., Altomonte, M. and Maio, M. (2004) Intratumor heterogeneity of cancer/testis antigens expression in human cutaneous melanoma is methylation-regulated and functionally reverted by 5-aza-2'-deoxycytidine. Cancer Res. 64, 9167-9171.
- Antequera, F. and A. Bird (1993a) CpG islands. EXS. 64, 169-185.
- Antequera, F. and A. Bird (1993b) Number of CpG islands and genes in human and mouse. Proc. Natl. Acad. Sci. U.S.A. 90, 11995-11999.
- Dong, X., Yang, X., Wang, Y. and Chen, W. (2004) Zincfinger protein ZNF165 is a novel cancer-testis antigen capable of eliciting antibody response in hepatocellular carcinoma patients. Br. J. Cancer 91, 1566-1570.
- Loukinov, D., Pugacheva, E., Vatolin, S., Pack, S., Moon, H., Chernukhin, I., Mannan, P., Larsson, E., Kanduri, C., Vostrov, A., Cui, H., Niemitz, E., Rasko, J., Docquier, F., Kistler, M., Breen, J., Zhuang, Z., Quitschke, W., Renkawitz, R., Klenova, E., Feinberg, A., Ohlsson, R., Morse, H. R. and Lobanenkov, V. (2002) BORIS, a novel male germline-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proc. Natl. Acad. Sci. U.S.A. 99, 6806-6811.
- Lim, F., Soulez, M., Koczan, D., Thiesen, H. and Knight, J. (1998) A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas. Oncogene. 17, 2013-2018.
- Gama-Sosa, M., Slagel, V., Trewyn, R., Oxenhandler, R., Kuo, K., Gehrke, C. and Ehrlich, M. (1983) The 5-methylcytosine content of DNA from human tumors. Nucleic. Acids. Res. 11, 6883-6894.
- del Mazo, J., Prantera, G., Torres, M. and Ferraro, M. (1994) DNA methylation changes during mouse spermatogenesis. Chromosome Res. 2, 147-152.
- Zhu, J. and Yao, X. (2007) Use of DNA methylation for cancer detection and molecular classification. J. Biochem. Mol. Biol. 40, 135-141.
- Jones, P. and Baylin, S. (2002) The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3, 415-428.
- Sasaki, H. and Matsui, Y. (2008) Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat. Rev. Genet. 9, 129-140.
- Jones, P. and Takai, D. (2001) The role of DNA methylation in mammalian epigenetics. Science 293, 1068-1070.
- De Smet, C., De Backer, O., Faraoni, I., Lurquin, C., Brasseur, F. and Boon, T. (1996) The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc. Natl. Acad. Sci. U.S.A. 93, 7149-7153.
- Iguchi-Ariga, S. and Schaffner, W. (1989) CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev. 3, 612-619.
- Coral, S., Sigalotti, L., Altomonte, M., Engelsberg, A., Colizzi, F., Cattarossi, I., Maraskovsky, E., Jager, E., Seliger, B. and Maio, M. (2002) 5-aza-2'-deoxycytidine-induced expression of functional cancer testis antigens in human renal cell carcinoma: immunotherapeutic implications. Clin. Cancer. Res. 8, 2690-2695.
- Christman, J. (2002) 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene. 21, 5483-5495.
- James, S., Link, P. and Karpf, A. (2006) Epigenetic regulation of X-linked cancer/germline antigen genes by DNMT1 and DNMT3b. Oncogene. 25, 6975-6985.
- Coral, S., Sigalotti, L., Gasparollo, A., Cattarossi, I., Visintin, A., Cattelan, A., Altomonte, M. and Maio, M. (1999) Prolonged upregulation of the expression of HLA class I antigens and costimulatory molecules on melanoma cells treated with 5-aza-2'-deoxycytidine (5-AZA-CdR). J. Immunother 22, 16-24.
- Sambrook, J., Fritsch, E. F. and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, New York, USA.
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