Demethylation of CpG islands in the 5' upstream regions mediates the expression of the human testis-specific gene MAGEB16 and its mouse homolog Mageb16
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Tissue-specific gene expression is regulated by epigenetic modification involving trans-acting factors. Here, we identifiedthat the human MAGEB16 gene and its mouse homolog,Mageb16, are only expressed in the testis. To investigate themechanism governing their expression, the promoter methylationstatus of these genes was examined in different samples. Two CpG islands (CGIs) in the 5' upstream region of MAGEB16were highly demethylated in human testes, whereas they weremethylated in cells without MAGEB16 expression. Similarly, theCGI in Mageb16 was hypomethylated in mouse testes buthypermethylated in other tissues and cells without Mageb16expression. Additionally, the expression of these genes could beactivated by treatment with the demethylation agent 5'-aza-2'-deoxycytidine (5'-aza-CdR). Luciferase assays revealed that bothgene promoter activities were inhibited by methylation of theCGI regions. Therefore, we propose that the testis-specificexpression of MAGEB16 and Mageb16 is regulated by themethylation status of their promoter regions.
Abstract
Tissue-specific gene expression is regulated by epigenetic modification involving trans-acting factors. Here, we identifiedthat the human MAGEB16 gene and its mouse homolog,Mageb16, are only expressed in the testis. To investigate themechanism governing their expression, the promoter methylationstatus of these genes was examined in different samples. Two CpG islands (CGIs) in the 5' upstream region of MAGEB16were highly demethylated in human testes, whereas they weremethylated in cells without MAGEB16 expression. Similarly, theCGI in Mageb16 was hypomethylated in mouse testes buthypermethylated in other tissues and cells without Mageb16expression. Additionally, the expression of these genes could beactivated by treatment with the demethylation agent 5'-aza-2'-deoxycytidine (5'-aza-CdR). Luciferase assays revealed that bothgene promoter activities were inhibited by methylation of theCGI regions. Therefore, we propose that the testis-specificexpression of MAGEB16 and Mageb16 is regulated by themethylation status of their promoter regions.
참고문헌 (20)
- Schultz, N., "A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets", Proc. Natl. Acad. Sci. U.S.A, 100, pp.12201~12206 (2003)
- Koslowski, M., "The human X chromosome is enriched for germline genes expressed in premeiotic germ cells of both sexes", Hum. Mol. Genet, 15, pp.2392~2399 (2006)
- van der Bruggen, P., "A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma", Science, 254, pp.1643~1647 (1991)
- Osterlund, C., "Mage-b4, a novel melanoma antigen (MAGE) gene specifically expressed during germ cell differentiation", Cancer Res, 60, pp.1054~1061 (2000)
- Chomez, P., "An overview of the MAGE gene family with the identification of all human members of the family", Cancer Res, 61, pp.5544~5551 (2001)
- Zhao, Q., "Differential evolution of MAGE genes based on expression pattern and selection pressure", PloS One, 7, pp.e48240~ (2012)
- Gure, A. O., "Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer", Clin. Cancer Res, 11, pp.8055~8062 (2005)
- Kim, J., "The clinical significance of MAGEA3 expression in pancreatic cancer", Int. J. Cancer, 118, pp.2269~2275 (2006)
- De Smet, C., "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, pp.7327~7335 (1999)
- De Smet, C., "Promoter-dependent mechanism leading to selective hypomethylation within the 5' region of gene MAGE-A1 in tumor cells", Mol. Cell. Biol, 24, pp.4781~4790 (2004)
- Pattani, K. M., "MAGEB2 is activated by promoter demethylation in head and neck squamous cell carcinoma", PloS One, 7, pp.e45534~ (2012)
- Zhang, J., "A novel protein-DNA interaction involved with the CpG dinucleotide at -30 upstream is linked to the DNA methylation mediated transcription silencing of the MAGE-A1 gene", Cell Res, 14, pp.283~294 (2004)
- Gang Bai, "Promoter demethylation mediates the expression of ZNF645, a novel cancer", testis gene, 2010, pp.43(6), 400~406[DOI]
- Dong, X., "Zinc- finger protein ZNF165 is a novel cancer-testis antigen capable of eliciting antibody response in hepatocellular carcinoma patients", Br. J. Cancer, 91, pp.1566~1570 (2004)
- Gaspar, J. A., "Gene expression signatures defining fundamental biological processes in pluripotent, early, and late differentiated embryonic stem cells", Stem Cells Dev, 21, pp.2471~2484 (2012)
- Sasaki, H, "Epigenetic events in mammalian germ-cell development: reprogramming and beyond", Nat. Rev. Genet, 9, pp.129~140 (2008)
- del Mazo, J., "DNA methylation changes during mouse spermatogenesis", Chromosome Res, 2, pp.147~152 (1994)
- Zhu, W. G., "Methylation of adjacent CpG sites affects Sp1", Sp3 binding and activity in the p21(Cip1) promoter, 2003, pp.23, 4056~4065
- Iguchi-Ariga, S., "CpG methylation of the cAMP-responsive enhancer", promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation, 1989, pp.3, 612~619
- Maraskovsky, E., "5'-aza-2'-deoxycytidine induced expression of functional cancer testis antigens in human renal cell carcinoma: immunotherapeutic implications", Clin. Cancer. Res, 8, pp.2690~2695 (2002)