#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Transgenerational Inheritance of Diet-Induced Genome Rearrangements in Drosophila


We show that altering the nutritional medium of Drosophila cultures, emulating dietary largess in the wild, increases expression of the high copy-number ribosomal RNA genes and results in rDNA instability and loss. The reduction in gene copy number occurs both in somatic and germ cells, such that altered copy numbers are transmitted to the next generation. Our findings have clear ecological and disease relevance. The reduction of supernumerary ribosomal RNA gene copy number has been previously shown to compromise both epigenetic and genomic stability and alter the expression of hundreds of genes, while rDNA instability itself is a key progression hallmark of some cancers. This study links diet and Insulin/Insulin-like Signaling modulation to changes in the genome and provides an accounting for natural copy number variation of rRNA genes.


Vyšlo v časopise: Transgenerational Inheritance of Diet-Induced Genome Rearrangements in Drosophila. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005148
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005148

Souhrn

We show that altering the nutritional medium of Drosophila cultures, emulating dietary largess in the wild, increases expression of the high copy-number ribosomal RNA genes and results in rDNA instability and loss. The reduction in gene copy number occurs both in somatic and germ cells, such that altered copy numbers are transmitted to the next generation. Our findings have clear ecological and disease relevance. The reduction of supernumerary ribosomal RNA gene copy number has been previously shown to compromise both epigenetic and genomic stability and alter the expression of hundreds of genes, while rDNA instability itself is a key progression hallmark of some cancers. This study links diet and Insulin/Insulin-like Signaling modulation to changes in the genome and provides an accounting for natural copy number variation of rRNA genes.


Zdroje

1. Anway M.D., et al., Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science, 2005. 308(5727): p. 1466–9. 15933200

2. Jirtle R.L. and Skinner M.K., Environmental epigenomics and disease susceptibility. Nat Rev Genet, 2007. 8(4): p. 253–62. 17363974

3. Arico J.K., et al., Epigenetic Patterns Maintained in Early Caenorhabditis elegans Embryos Can Be Established by Gene Activity in the Parental Germ Cells. PLoS Genet, 2011. 7(6): p. e1001391. doi: 10.1371/journal.pgen.1001391 21695223

4. Feil R. and Fraga M.F., Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet, 2011. 13(2): p. 97–109. doi: 10.1038/nrg3142 22215131

5. Greer E.L., et al., Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature, 2011. 479(7373): p. 365–71. doi: 10.1038/nature10572 22012258

6. Seong K.H., et al., Inheritance of stress-induced, ATF-2-dependent epigenetic change. Cell, 2011. 145(7): p. 1049–61. doi: 10.1016/j.cell.2011.05.029 21703449

7. Crews D., et al., Epigenetic transgenerational inheritance of altered stress responses. Proc Natl Acad Sci U S A, 2012. 109(23): p. 9143–8. doi: 10.1073/pnas.1118514109 22615374

8. Padmanabhan N., et al., Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development. Cell, 2013. 155(1): p. 81–93. doi: 10.1016/j.cell.2013.09.002 24074862

9. Ahmad K. and Henikoff S., Epigenetic consequences of nucleosome dynamics. Cell, 2002. 111(3): p. 281–4. 12419239

10. Deal R.B., Henikoff J.G., and Henikoff S., Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones. Science, 2010. 328(5982): p. 1161–4. doi: 10.1126/science.1186777 20508129

11. Hathaway N.A., et al., Dynamics and memory of heterochromatin in living cells. Cell, 2012. 149(7): p. 1447–60. doi: 10.1016/j.cell.2012.03.052 22704655

12. Teves S.S., Deal R.B., and Henikoff S., Measuring genome-wide nucleosome turnover using CATCH-IT. Methods Enzymol, 2012. 513: p. 169–84. doi: 10.1016/B978-0-12-391938-0.00007-0 22929769

13. Ptashne M., Epigenetics: core misconcept. Proc Natl Acad Sci U S A, 2013. 110(18): p. 7101–3. doi: 10.1073/pnas.1305399110 23584020

14. Struhl K., Is DNA methylation of tumour suppressor genes epigenetic? Elife, 2014. 3: p. e02475. doi: 10.7554/eLife.02475 24623307

15. Ahmad K. and Golic K.G., Somatic reversion of chromosomal position effects in Drosophila melanogaster. Genetics, 1996. 144(2): p. 657–70. 8889528

16. Conconi A., et al., Two different chromatin structures coexist in ribosomal RNA genes throughout the cell cycle. Cell, 1989. 57(5): p. 753–61. 2720786

17. Riddle N.C. and Richards E.J., Genetic variation in epigenetic inheritance of ribosomal RNA gene methylation in Arabidopsis. Plant J, 2005. 41(4): p. 524–32. 15686517

18. Eickbush D.G., et al., Epigenetic regulation of retrotransposons within the nucleolus of Drosophila. Mol Cell Biol, 2008. 28(20): p. 6452–61. doi: 10.1128/MCB.01015-08 18678644

19. Grummt I. and Langst G., Epigenetic control of RNA polymerase I transcription in mammalian cells. Biochim Biophys Acta, 2013. 1829(3–4): p. 393–404.

20. Warner J.R., The economics of ribosome biosynthesis in yeast. Trends Biochem Sci, 1999. 24(11): p. 437–40. 10542411

21. Pellegrini M., Manning J., and Davidson N., Sequence arrangement of the rDNA of Drosophila melanogaster. Cell, 1977. 10(2): p. 213–4. 402223

22. French S.L., et al., In exponentially growing Saccharomyces cerevisiae cells, rRNA synthesis is determined by the summed RNA polymerase I loading rate rather than by the number of active genes. Mol Cell Biol, 2003. 23(5): p. 1558–68. 12588976

23. Peng J.C. and Karpen G.H., H3K9 methylation and RNA interference regulate nucleolar organization and repeated DNA stability. Nat Cell Biol, 2007. 9(1): p. 25–35. 17159999

24. Paredes S. and Maggert K.A., Ribosomal DNA contributes to global chromatin regulation. Proc Natl Acad Sci U S A, 2009. 106(42): p. 17829–34. doi: 10.1073/pnas.0906811106 19822756

25. Guerrero P.A. and Maggert K.A., The CCCTC-binding factor (CTCF) of Drosophila contributes to the regulation of the ribosomal DNA and nucleolar stability. PLoS One, 2011. 6(1): p. e16401. doi: 10.1371/journal.pone.0016401 21283722

26. Larson K., et al., Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet, 2012. 8(1): p. e1002473. doi: 10.1371/journal.pgen.1002473 22291607

27. Saka K., et al., Cellular senescence in yeast is regulated by rDNA noncoding transcription. Curr Biol, 2013. 23(18): p. 1794–8. doi: 10.1016/j.cub.2013.07.048 23993840

28. Cohen S., Yacobi K., and Segal D., Extrachromosomal circular DNA of tandemly repeated genomic sequences in Drosophila. Genome Res, 2003. 13(6A): p. 1133–45. 12799349

29. Takeuchi Y., Horiuchi T., and Kobayashi T., Transcription-dependent recombination and the role of fork collision in yeast rDNA. Genes Dev, 2003. 17(12): p. 1497–506. 12783853

30. Tartof K.D., Unequal mitotic sister chromatid exchange and disproportionate replication as mechanisms regulating ribosomal RNA gene redundancy. Cold Spring Harb Symp Quant Biol, 1974. 38: p. 491–500. 4208791

31. Hawley R.S. and Tartof K.D., A two-stage model for the control of rDNA magnification. Genetics, 1985. 109(4): p. 691–700. 3921426

32. Bianciardi A., et al., Ribosomal DNA organization before and after magnification in Drosophila melanogaster. Genetics, 2012. 191(3): p. 703–23. doi: 10.1534/genetics.112.140335 22505623

33. Dawid I.B., Wellauer P.K., and Long E.O., Ribosomal DNA in Drosophila melanogaster. I. Isolation and characterization of cloned fragments. J Mol Biol, 1978. 126(4): p. 749–68. 106128

34. Long E.O. and Dawid I.B., Repeated genes in eukaryotes. Annu Rev Biochem, 1980. 49: p. 727–64. 6996571

35. Lyckegaard E.M. and Clark A.G., Ribosomal DNA and Stellate gene copy number variation on the Y chromosome of Drosophila melanogaster. Proc Natl Acad Sci U S A, 1989. 86(6): p. 1944–8. 2494656

36. Stage D.E. and Eickbush T.H., Sequence variation within the rRNA gene loci of 12 Drosophila species. Genome Res, 2007. 17(12): p. 1888–97. 17989256

37. Boulon S., et al., The nucleolus under stress. Mol Cell, 2010. 40(2): p. 216–27. doi: 10.1016/j.molcel.2010.09.024 20965417

38. Ide S., et al., Abundance of ribosomal RNA gene copies maintains genome integrity. Science, 2010. 327(5966): p. 693–6. doi: 10.1126/science.1179044 20133573

39. Boyd M.T., Vlatkovic N., and Rubbi C.P., The nucleolus directly regulates p53 export and degradation. J Cell Biol, 2011. 194(5): p. 689–703. doi: 10.1083/jcb.201105143 21893597

40. Kobayashi T., Regulation of ribosomal RNA gene copy number and its role in modulating genome integrity and evolutionary adaptability in yeast. Cell Mol Life Sci, 2011. 68(8): p. 1395–403. doi: 10.1007/s00018-010-0613-2 21207101

41. Paredes S., The Ribosomal DNA Genes Influence Genome-Wide Gene Expression in Drosophila melanogaster., in Biology. 2011, Texas A&M University. p. 175. doi: 10.1016/j.jphotobiol.2011.08.009 21955546

42. Tsurumi A. and Li W.X., Global heterochromatin loss: a unifying theory of aging? Epigenetics, 2012. 7(7): p. 680–8. doi: 10.4161/epi.20540 22647267

43. Zhou J S.T., Martinsen L, Lemos B, Eickbush TH, Hartl DL, Y chromosome mediates ribosomal DNA silencing and modulates the chromatin state in Drosophila. Proc Natl Acad Sci U S A, 2012. doi: 10.1073/pnas.1207367109(Online).

44. Chen S., et al., Repression of RNA polymerase I upon stress is caused by inhibition of RNA-dependent deacetylation of PAF53 by SIRT7. Mol Cell, 2013. 52(3): p. 303–13. doi: 10.1016/j.molcel.2013.10.010 24207024

45. Grummt I., The nucleolus-guardian of cellular homeostasis and genome integrity. Chromosoma, 2013. 122(6): p. 487–97. 24022641

46. Gibbons J.G., et al., Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans. Nat Commun, 2014. 5: p. 4850. doi: 10.1038/ncomms5850 25209200

47. Maggert K.A., Genetics: polymorphisms, epigenetics, and something in between. Genet Res Int, 2012. 2012: p. 867951. doi: 10.1155/2012/867951 22567405

48. Grummt I. and Ladurner A.G., A metabolic throttle regulates the epigenetic state of rDNA. Cell, 2008. 133(4): p. 577–80. doi: 10.1016/j.cell.2008.04.026 18485866

49. Murayama A., et al., Epigenetic control of rDNA loci in response to intracellular energy status. Cell, 2008. 133(4): p. 627–39. doi: 10.1016/j.cell.2008.03.030 18485871

50. Smith D.L. Jr., et al., Calorie restriction effects on silencing and recombination at the yeast rDNA. Aging Cell, 2009. 8(6): p. 633–42. doi: 10.1111/j.1474-9726.2009.00516.x 19732044

51. Fontana L., Partridge L., and Longo V.D., Extending healthy life span—from yeast to humans. Science, 2010. 328(5976): p. 321–6. doi: 10.1126/science.1172539 20395504

52. Grandison R.C., et al., Effect of a standardised dietary restriction protocol on multiple laboratory strains of Drosophila melanogaster. PLoS One, 2009. 4(1): p. e4067. doi: 10.1371/journal.pone.0004067 19119322

53. Zhou J., et al., Y chromosome mediates ribosomal DNA silencing and modulates the chromatin state in Drosophila. Proc Natl Acad Sci U S A, 2012. 109(25): p. 9941–6. doi: 10.1073/pnas.1207367109 22665801

54. Zhang Q., Shalaby N.A., and Buszczak M., Changes in rRNA transcription influence proliferation and cell fate within a stem cell lineage. Science, 2014. 343(6168): p. 298–301. doi: 10.1126/science.1246384 24436420

55. Paredes S. and Maggert K.A., Expression of I-CreI Endonuclease Generates Deletions Within the rDNA of Drosophila. Genetics, 2009. 181(4): p. 1661–71. doi: 10.1534/genetics.108.099093 19171942

56. Paredes S., et al., Ribosomal DNA deletions modulate genome-wide gene expression: "rDNA-sensitive" genes and natural variation. PLoS Genet, 2011. 7(4): p. e1001376. doi: 10.1371/journal.pgen.1001376 21533076

57. Aldrich J.C. and Maggert K.A., Quantitative PCR reveals naturally occurring and mutationally-induced repetitive sequence variation on the Drosophila Y chromosome. PLoS ONE, 2014. 9: e109906. doi: 10.1371/journal.pone.0109906 25285439

58. Maggert, K.A., Reduced rDNA Copy Number Does Not Affect "Competitive" Chromosome Pairing in XYY Males of Drosophila melanogaster. G3 (Bethesda), 2014.

59. Karpen G.H., Schaefer J.E., and Laird C.D., A Drosophila rRNA gene located in euchromatin is active in transcription and nucleolus formation. Genes Dev, 1988. 2(12B): p. 1745–63. 3149250

60. Peng J.C. and Karpen G.H., Epigenetic regulation of heterochromatic DNA stability. Curr Opin Genet Dev, 2008. 18(2): p. 204–11. doi: 10.1016/j.gde.2008.01.021 18372168

61. Spofford J.B., Position-effect variegation in Drosophila, in The Genetics and Biology of Drosophila, Ashburner M. and Novitski E., Editors. 1976, Academic Press. p. 955–1019.

62. Ashburner M., Golic K.G., and Hawley R.S., Drosophila: a laboratory handbook. 2nd ed. 2005, Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press. xxviii, 1409 p.

63. Lemos B., Araripe L.O., and Hartl D.L., Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences. Science, 2008. 319(5859): p. 91–3. doi: 10.1126/science.1148861 18174442

64. Jiang P.P., Hartl D.L., and Lemos B., Y Not a Dead End: Epistatic Interactions Between Y-linked Regulatory Polymorphisms and Genetic Background Affect Global Gene Expression in Drosophila melanogaster. Genetics, 2010.

65. Kwan E.X., et al., A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan. PLoS Genet, 2013. 9(3): p. e1003329. doi: 10.1371/journal.pgen.1003329 23505383

66. Jakubczak J.L., et al., Turnover of R1 (type I) and R2 (type II) retrotransposable elements in the ribosomal DNA of Drosophila melanogaster. Genetics, 1992. 131(1): p. 129–42. 1317313

67. Eickbush T.H., et al., Evolution of R1 and R2 in the rDNA units of the genus Drosophila. Genetica, 1997. 100(1–3): p. 49–61. 9440280

68. Grewal S.S., Evans J.R., and Edgar B.A., Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway. J Cell Biol, 2007. 179(6): p. 1105–13. 18086911

69. Grewal S.S., Insulin/TOR signaling in growth and homeostasis: a view from the fly world. Int J Biochem Cell Biol, 2009. 41(5): p. 1006–10. doi: 10.1016/j.biocel.2008.10.010 18992839

70. Rosby R., et al., Knockdown of the Drosophila GTPase nucleostemin 1 impairs large ribosomal subunit biogenesis, cell growth, and midgut precursor cell maintenance. Mol Biol Cell, 2009. 20(20): p. 4424–34. doi: 10.1091/mbc.E08-06-0592 19710426

71. Greil F. and Ahmad K., Nucleolar Dominance of the Y Chromosome in Drosophila melanogaster. Genetics, 2012.

72. Bjedov I., et al., Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab, 2010. 11(1): p. 35–46. doi: 10.1016/j.cmet.2009.11.010 20074526

73. Ueishi S., Shimizu H., and H.I Y, Male germline stem cell division and spermatocyte growth require insulin signaling in Drosophila. Cell Struct Funct, 2009. 34(1): p. 61–9. 19384053

74. Wang L., McLeod C.J., and Jones D.L., Regulation of adult stem cell behavior by nutrient signaling. Cell Cycle, 2011. 10(16): p. 2628–34. 21814033

75. Endow S.A., Molecular characterization of ribosomal genes on the Ybb- chromosome of Drosophila melanogaster. Genetics, 1982. 102(1): p. 91–9. 6813192

76. Ritossa F.M., Unstable redundancy of genes for ribosomal RNA. Proc Natl Acad Sci U S A, 1968. 60(2): p. 509–16. 5248808

77. Kobayashi T., A new role of the rDNA and nucleolus in the nucleus—rDNA instability maintains genome integrity. Bioessays, 2008. 30(3): p. 267–72. doi: 10.1002/bies.20723 18293366

78. Sackton T.B., et al., Interspecific Y chromosome introgressions disrupt testis-specific gene expression and male reproductive phenotypes in Drosophila. Proc Natl Acad Sci U S A, 2011. 108(41): p. 17046–51. doi: 10.1073/pnas.1114690108 21969588

79. Tartof K.D., Regulation of ribosomal RNA gene multiplicity in Drosophila melanogaster. Genetics, 1973. 73(1): p. 57–71. 4631601

80. Endow S.A. and Glover D.M., Differential replication of ribosomal gene repeats in polytene nuclei of Drosophila. Cell, 1979. 17(3): p. 597–605. 113105

81. Schneeberger R.G. and Cullis C.A., Specific DNA alterations associated with the environmental induction of heritable changes in flax. Genetics, 1991. 128(3): p. 619–30. 1678726

82. Montanaro L., Trere D., and Derenzini M., Nucleolus, ribosomes, and cancer. Am J Pathol, 2008. 173(2): p. 301–10. doi: 10.2353/ajpath.2008.070752 18583314

83. Derenzini M., Montanaro L., and Trere D., What the nucleolus says to a tumour pathologist. Histopathology, 2009. 54(6): p. 753–62. doi: 10.1111/j.1365-2559.2008.03168.x 19178588

84. Drygin D., Rice W.G., and Grummt I., The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer. Annu Rev Pharmacol Toxicol, 2010. 50: p. 131–56. doi: 10.1146/annurev.pharmtox.010909.105844 20055700

85. McStay B. and Grummt I., The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol, 2008. 24: p. 131–57. doi: 10.1146/annurev.cellbio.24.110707.175259 18616426

86. Grummt I., The nucleolus-guardian of cellular homeostasis and genome integrity. Chromosoma, 2013.

87. Wei K.H., et al., Correlated variation and population differentiation in satellite DNA abundance among lines of Drosophila melanogaster. Proc Natl Acad Sci U S A, 2014. 111(52): p. 18793–8. doi: 10.1073/pnas.1421951112 25512552

88. Maggert K.A. and Golic K.G., Highly efficient sex chromosome interchanges produced by I-CreI expression in Drosophila. Genetics, 2005. 171(3): p. 1103–14. 16020774

89. Wu Q., et al., Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc Natl Acad Sci U S A, 2005. 102(37): p. 13289–94. 16150727

90. Clancy D.J. and Kennington W.J., A simple method to achieve consistent larval density in bottle cultures. Drosophila Information Service, 2001. 84: p. 168–169.

91. Winkles J.A., Phillips W.H., and Grainger R.M., Drosophila ribosomal RNA stability increases during slow growth conditions. J Biol Chem, 1985. 260(12): p. 7716–20. 3922989

92. Shimada H., et al., Normalization using ploidy and genomic DNA copy number allows absolute quantification of transcripts, proteins and metabolites in cells. Plant Methods, 2010. 6: p. 29. doi: 10.1186/1746-4811-6-29 21190547

93. Ramakers C., et al., Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett, 2003. 339(1): p. 62–6. 12618301

94. Pfaffl M.W., A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res, 2001. 29(9): p. e45. 11328886

95. Bogart K. and Andrews J., Extraction of Total RNA from Drosophila, in CGB Technical Report 2006–10. 2006, The Center for Genomics and Bioinformatics, Indiana University, Bloomington, Indiana.

96. Krzywinski M. and Altman N., Points of significance: error bars. Nat Methods, 2013. 10(10): p. 921–2. doi: 10.1038/nmeth.2659 24161969

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#