BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Role of telomere length in subtelomeric gene expression and its possible relation to cellular senescence

  • Hernandez-Caballero, E. (Unidad de Investigacion Medica en Genetica Humana, Centro Medico Nacional Siglo XXI (CMN SXXI), Instituto Mexicano del Seguro Social (IMSS)) ;
  • Herrera-Gonzalez, N.E. (Escuela Superior de Medicina, Instituto Politecnico Nacional (IPN)) ;
  • Salamanca-Gomez, F. (Unidad de Investigacion Medica en Genetica Humana, Centro Medico Nacional Siglo XXI (CMN SXXI), Instituto Mexicano del Seguro Social (IMSS)) ;
  • Arenas-Aranda, D.J. (Unidad de Investigacion Medica en Genetica Humana, Centro Medico Nacional Siglo XXI (CMN SXXI), Instituto Mexicano del Seguro Social (IMSS))
  • Published : 2009.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Transcriptional silencing of subtelomeric genes is associated with telomere length, which is correlated with age. Long and short telomeres in young and old people, respectively, coincide with gene repression and activation in each case. In addition, differential location of genes with respect to telomeres causes telomere position effect. There is very little evidence of the manner in which age-related telomere length affects the expression of specific human subtelomeric genes. We analyzed the relationship between telomere length and gene expression levels in fibroblasts derived from human donors at ages ranging from 0-70 years. We studied three groups of genes located between 100 and 150 kb, 200 and 250 kb, and >300 kb away from telomeres. We found that the chromatin modifier-encoding genes Eu-HMTase1, ZMYND11, and RASA3 were overexpressed in adults. Our results suggest that short telomere length-related overexpression of chromatin modifiers could underlie transcriptional changes contributing to cellular senescence.

Keywords

References

  1. Greider, C. W. (1996) Telomere length regulation. Annu. Rev. Biochem. 65, 337-365 https://doi.org/10.1146/annurev.bi.65.070196.002005
  2. Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H. and de Lange, T. (1999) Mammalian telomeres end in a large duplex loop. Cell 97, 503-514 https://doi.org/10.1016/S0092-8674(00)80760-6
  3. De Lange, T. (2002) Protection of mammalian telomeres. Oncogene. 21, 532-540 https://doi.org/10.1038/sj.onc.1205080
  4. McEachern, M. J., Krauskopf, A. and Blackburn, E. H. (2000) Telomeres and their control. Annu. Rev. Genet. 34, 331-358 https://doi.org/10.1146/annurev.genet.34.1.331
  5. Sherr, C. J. and DePinho, R. A. (2000) Cellular senescence: Mitotic clock or culture shock? Cell 102, 407-410 https://doi.org/10.1016/S0092-8674(00)00046-5
  6. Perrod, S. and Gasser, S. M. (2003) Long-range silencing and position effects at telomeres and centromeres: parallels and differences. Cell. Mol. Life Sci. 60, 2303-2318 https://doi.org/10.1007/s00018-003-3246-x
  7. Wright, W. E. and Shay, J. W. (1992) Telomere positional effects and the regulation of cellular senescence. Trends Genet. 8, 193-197 https://doi.org/10.1016/0168-9525(92)90232-S
  8. Louis, E. J. and Vershinin, A. V. (2005) Chromosome ends:different sequences may provide conserved functions. ByoEssays. 27, 685-697 https://doi.org/10.1002/bies.20259
  9. Zhu, J. and Yao, X. (2007) Use of DNA methylation for cancer detection and molecular classification. J. Biochem. Mol. Biol. 40, 135-141 https://doi.org/10.5483/BMBRep.2007.40.2.135
  10. Ottaviani, A., Gilson, E. and Magdinier, F. (2008) Telomeric position effect: from the yeast paradigm to human pathologies? Biochimie. 90, 93-107 https://doi.org/10.1016/j.biochi.2007.07.022
  11. Wood, J. G. and Sinclair, D. A. (2002) TPE or not TPE? It's no longer a question. TRENDS Pharmacol. Sci. 23, 1-4 https://doi.org/10.1016/S0165-6147(00)01891-5
  12. Ning, Y., Xu, J. F., Li, Y., Chavez L., Riethman, H. C., Lansdorp, P. M. and Weng, N. P. (2003) Telomere length and the expression of natural telomeric genes in human fibroblasts. Hum. Mol. Genet. 12, 1329-1336 https://doi.org/10.1093/hmg/ddg139
  13. Rubin, H. (1997) Cell aging in vivo and in vitro. Mech. Ageing Dev. 98, 1-35 https://doi.org/10.1016/S0047-6374(97)00067-5
  14. Stewart, S. A., Ben-Porath, I., Carey, V. J., O'Connor, B. F., Hahn, W. C. and Weinberg, R. A. (2003) Erosion of the telomeric single-strand overhang at replicative senescence. Nat. Genet. 33, 492-496 https://doi.org/10.1038/ng1127
  15. Palmero, I., McConell, B., Rarry, D., Brookes, S., Hara, E., Bates, S., Jat, P. and Peters, G. (1997) Accumulation of p16INK4a in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status. Oncogene. 15, 495-503 https://doi.org/10.1038/sj.onc.1201212
  16. Smogorzewska, A. and de Lange, T. (2002) Different telomere damage signaling pathways in human and mouse cells. EMBO J. 21, 4338-4348 https://doi.org/10.1093/emboj/cdf433
  17. Aparicio, O. M. and Gottchling, D. E. (1994) Overcoming telomeric silencing: a trans-activator competes to establish gene expression in cell cycle dependent way. Genes Dev. 8, 1133-1146 https://doi.org/10.1101/gad.8.10.1133
  18. Fourel, G., Lebrun, E. and Gilson, E. (2002) Protosilencers as building blocks for heterochromatin. BioEssays. 24, 828-835 https://doi.org/10.1002/bies.10139
  19. Cullen, P. J., Hsuan, J. J., Truong, O., Letcher, A. J., Jackson, T. R., Dawson, A. P. and Irvine, R. F. (1995) Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family. Nature 376, 527-530 https://doi.org/10.1038/376527a0
  20. Velasco, G., Grkovic, S. and Ansieau, S. (2006) New insights into BS69 functions. J. Biol. Chem. 281, 16546-16550 https://doi.org/10.1074/jbc.M600573200
  21. Tachibana, M., Ueda, J., Fukuda, M., Takeda, N., Ohta, T., Iwanari, H., Sakihama, T., Kodama, T., Hamakubo, T. and Shinkai, Y. (2005) Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes & Dev. 19, 815-826 https://doi.org/10.1101/gad.1284005
  22. Gross-Bellard, M., Oudet, P. and Chambon, P. (1973) Isolation of high-molecular-weight DNA from mammalian cells. Eur. J. Biochem. 36, 32-38 https://doi.org/10.1111/j.1432-1033.1973.tb02881.x
  23. Baur, J. A., Zou, Y., Shay, J. W. and Wright, W. E. (2001) Telomere position effect in human cells. Science 292, 2075-2077 https://doi.org/10.1126/science.1062329
  24. Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O., Peacocke, M. and Campisi, J. (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. U.S.A. 92, 9363-9367 https://doi.org/10.1073/pnas.92.20.9363
  25. Satyanarayana, A. and Rudolph, K. L. (2004) p16 and ARF:activation of teenage proteins in old age. J. Clin. Invest. 114, 1237-1240 https://doi.org/10.1172/JCI23437

Cited by

  1. Telomere Length of Individual Chromosomes in Patients with Rheumatoid Arthritis vol.160, pp.6, 2016, https://doi.org/10.1007/s10517-016-3308-3
  2. MicroRNAs as a novel cellular senescence regulator vol.11, pp.1, 2012, https://doi.org/10.1016/j.arr.2011.06.001
  3. Computel: Computation of Mean Telomere Length from Whole-Genome Next-Generation Sequencing Data vol.10, pp.4, 2015, https://doi.org/10.1371/journal.pone.0125201
  4. Muscular dystrophy in the mdx mouse is a severe myopathy compounded by hypotrophy, hypertrophy and hyperplasia vol.5, pp.1, 2015, https://doi.org/10.1186/s13395-015-0041-y
  5. General RBP expression in human tissues as a function of age vol.11, pp.4, 2012, https://doi.org/10.1016/j.arr.2012.01.005
  6. Telomere Length Maintenance and Cardio-Metabolic Disease Prevention Through Exercise Training vol.46, pp.9, 2016, https://doi.org/10.1007/s40279-016-0482-4
  7. DISIS: Prediction of Drug Response through an Iterative Sure Independence Screening vol.10, pp.3, 2015, https://doi.org/10.1371/journal.pone.0120408