Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Single Nucleotide Polymorphism in the Promoter Region of H1 Histone Family Member N, Testis-specific (H1FNT) and Its Association Study with Male Infertility

  • Yang, Seung-Hee (Functional Genomics Lab, Cell and Gene Therapy Research Institute, School of Medicine, CHA University) ;
  • Lee, Jin-U (Department of Pharmacology, School of Medicine, CHA University) ;
  • Lee, Su-Man (Functional Genomics Lab, Cell and Gene Therapy Research Institute, School of Medicine, CHA University)
  • Accepted : 2010.12.08
  • Published : 2010.12.31
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Abstract

The H1 histone family, member N, testis-specific (H1FNT) is exclusively expressed in the testis, and had its possible role for sperm chromatin formation. The purpose of this study is to investigate any genetic association of H1FNT gene with male infertility, especially at the promoter region. We examined the promoter single nucleotide polymorphisms (SNP) of H1FNT gene which is located within transcription factor binding site for its association with male infertility. The statistical analysis showed that the -1129A>T polymorphism was present at a statistically significance in male infertility (p=0.0059 and 0.0349 for hetero and risk type, respectively). The dual-luciferase promoter assay was performed to examine the polymorphic effect of this promoter SNP by the cloning of promoter region (1700bp fragment) into pGL3-basic vector. In our plasmid based reporter system, there is no big difference between wild and risk type. In conclusion, H1FNT -1129A>T promoter SNP is statistically significant with male infertility, especially with subfertile (non-azoospermia) group. Further analysis of its functional polymorphic effect in vivo may provide the biological significance of testis-specific histone with spermatogenesis.

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References

  1. WHO (2001), Laboratory manual of the WHO for the examination of human semen and sperm-cervical mucus interaction, I-XII, 1-123 pp. 2001/10/30 ed. Ann. Ist. Super Sanita 37.
  2. Heinemeyer, T., Chen, X., Karas, H., Kel, A.E., Kel, O.V., Liebich, I., Meinhardt, T., Reuter, I., Schacherer, F., and Wingender, E. (1999). Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms. Nucl. Acids Res. 27, 318-322. https://doi.org/10.1093/nar/27.1.318
  3. Kimura, T., Ito, C., Watanabe, S., Takahashi, T., Ikawa, M., Yomogida, K., Fujita, Y., Ikeuchi, M., Asada, N., Matsumiya, K., Okuyama, A., Okabe, M., Toshimori, K.,and Nakano, T. (2003). Mouse germ cell-less as an essential component for nuclear integrity. Mol. Cell Biol. 23, 1304-1313. https://doi.org/10.1128/MCB.23.4.1304-1315.2003
  4. Martianov, I., Brancorsini, S., Catena, R., Gansmuller, A., Kotaja, N., Parvinen, M., Sassone-Corsi, P., and Davidson, I. (2005). Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis. Proc. Natl. Acad. Sci. USA 102, 2808-2813. https://doi.org/10.1073/pnas.0406060102
  5. Matys, V., Fricke, E., Geffers, R., Gossling, E., Haubrock, M., Hehl, R., Hornischer, K., Karas, D., Kel, A.E., Kel-Margoulis, O.V., Kloos, D.U., Land, S., Lewicki-Potapov, B., Michael, H., Munch, R., Reuter, I., Rotert, S., Saxel, H., Scheer, M., Thiele, S., and Wingender, E. (2003). TRANSFAC: transcriptional regulation, from patterns to profiles. Nucl. Acids Res. 31, 374-378. https://doi.org/10.1093/nar/gkg108
  6. Miyagawa, Y., Nishimura, H., Tsujimura, A., Matsuoka, Y., Matsumiya, K., Okuyama, A., Nishimune, Y., and Tanaka, H. (2005). Single-nucleotide polymorphisms and mutation analyses of the TNP1 and TNP2 genes of fertile and infertile human male populations. J. Androl. 26, 779-786. https://doi.org/10.2164/jandrol.05069
  7. Park, J.H., Lee, H.C., Jeong, Y.M., Chung, T.G., Kim, H.J., Kim, N.K., Lee, S.H., and Lee, S. (2005). MTHFR C677T polymorphism associates with unexplained infertile male factors. J. Assist. Reprod. Genet. 22, 361-368. https://doi.org/10.1007/s10815-005-6795-0
  8. Tanaka, H., Iguchi, N., Isotani, A., Kitamura, K., Toyama, Y., Matsuoka, Y., Onishi, M., Masai, K., Maekawa, M., Toshimori, K., Okabe, M., and Nishimune, Y. (2005). HANP1/H1T2, a novel histone H1-like protein involved in nuclear formation and sperm fertility. Mol. Cell Biol. 25, 7107-7119. https://doi.org/10.1128/MCB.25.16.7107-7119.2005
  9. Tanaka, H., Matsuoka, Y., Onishi, M., Kitamura, K., Miyagawa, Y., Nishimura, H., Tsujimura, A., Okuyama, A., and Nishimune, Y. (2006). Expression profiles and single-nucleotide polymorphism analysis of human HANP1/H1T2 encoding a histone H1-like protein. Int. J. Androl. 29, 353-359. https://doi.org/10.1111/j.1365-2605.2005.00600.x
  10. Tanaka, H., Miyagawa, Y., Tsujimura, A., Matsumiya, K., Okuyama, A., and Nishimune, Y. (2003). Single nucleotide polymorphisms in the protamine-1 and -2 genes of fertile and infertile human male populations. Mol. Hum. Reprod. 9, 69-73. https://doi.org/10.1093/molehr/gag010
  11. Yun, Y.J., Park, J.H., Song, S.H., and Lee, S. (2008). The association of 4a4b polymorphism of endothelial nitric oxide synthase (eNOS) gene with the sperm morphology in Korean infertile men. Fertil. Steril. 90, 1126-1131. https://doi.org/10.1016/j.fertnstert.2007.07.1382

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