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DDM1 guards against telomere truncation in Arabidopsis

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Abstract

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Prolonged hypomethylation of DNA leads to telomere truncation correlated with increased telomere recombination, transposon mobilization and stem cell death.

Abstract

Epigenetic pathways, including DNA methylation, are crucial for telomere maintenance. Deficient in DNA Methylation 1 (DDM1) encodes a nucleosome remodeling protein, required to maintain DNA methylation in Arabidopsis thaliana. Plants lacking DDM1 can be self-propagated, but in the sixth generation (G6) hypomethylation leads to rampant transposon activation and infertility. Here we examine the role of DDM1 in telomere length homeostasis through a longitudinal study of successive generations of ddm1-2 mutants. We report that bulk telomere length remains within the wild-type range for the first five generations (G1–G5), and then precipitously drops in G6. While telomerase activity becomes more variable in later generation ddm1-2 mutants, there is no correlation between enzyme activity and telomere length. Plants lacking DDM1 also exhibit no dysregulation of several known telomere-associated transcripts, including TERRA. Instead, telomere shortening coincides with increased G-overhangs and extra-chromosomal circles, consistent with deletional recombination. Telomere shortening also correlates with transcriptional activation of retrotransposons, and a hypersensitive DNA damage response in root apical meristems. Since abiotic stresses, including DNA damage, stimulate homologous recombination, we hypothesize that telomere deletion in G6 ddm1-2 mutants is a by-product of elevated genome-wide recombination in response to transposon mobilization. Further, we speculate that telomere truncation may be beneficial in adverse environmental conditions by accelerating the elimination of stem cells with aberrant genomes.

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References

  • Arnoult N, Van Beneden A, Decottignies A (2012) Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1alpha. Nat Struct Mol Biol 19:948–956

    Article  CAS  PubMed  Google Scholar 

  • Arora R, Lee Y, Wischnewski H, Brun CM, Schwarz T, Azzalin CM (2014) RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells. Nat Commun 5:5220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baubec T, Finke A, Scheid MO, Pecinka A (2014) Meristem-specific expression of epigenetic regulators safeguards transposon silencing in Arabidopsis. EMBO Rep 15:446–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bennetzen JL (2000) Transposable element contributions to plant gene and genome evolution. Plant Mol Biol 42:251–269

    Article  CAS  PubMed  Google Scholar 

  • Berardinelli F, Antoccia A, Cherubini R, De Nadal V, Gerardi S, Cirrone GA, Tanzarella C, Sgura A (2010) Transient activation of the ALT pathway in human primary fibroblasts exposed to high-LET radiation. Radiat Res 174:539–549

    Article  CAS  PubMed  Google Scholar 

  • Blackburn EH, Collins K (2011) Telomerase: an RNP enzyme synthesizes DNA. Cold Spring Harb Perspect Biol 3:a003558

    Article  PubMed  PubMed Central  Google Scholar 

  • Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nat Rev Genet 8:299–309

    Article  CAS  PubMed  Google Scholar 

  • Boltz KA, Leehy K, Song X, Nelson AD, Shippen DE (2012) ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity in Arabidopsis. Mol Biol Cell 23:1558–1568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brzeski J, Jerzmanowski A (2003) Deficient in DNA methylation 1 (DDM1) defines a novel family of chromatin-remodeling factors. J Biol Chem 278:823–828

    Article  CAS  PubMed  Google Scholar 

  • Cifuentes-Rojas C, Kannan K, Tseng L, Shippen DE (2011) Two RNA subunits and POT1a are components of Arabidopsis telomerase. Proc Natl Acad Sci USA 108:73–78

    Article  CAS  PubMed  Google Scholar 

  • Cifuentes-Rojas C, Nelson AD, Boltz KA, Kannan K, She X, Shippen DE (2012) An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage. Genes Dev 26:2512–2523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cokus SJ, Feng S, Zhang X, Chen Z, Merriman B, Haudenschild CD, Pradhan S, Nelson SF, Pellegrini M, Jacobsen SE (2008) Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452:215–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coluzzi E, Buonsante R, Leone S, Asmar AJ, Miller KL, Cimini D, Sgura A (2017) Transient ALT activation protects human primary cells from chromosome instability induced by low chronic oxidative stress. Sci Rep 7:43309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Lange T (2004) T-loops and the origin of telomeres. Nat Rev Mol Cell Biol 5:323–329

    Article  PubMed  Google Scholar 

  • Fairlie J, Harrington L (2015) Enforced telomere elongation increases the sensitivity of human tumour cells to ionizing radiation. DNA Repair 25:54–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finnegan EJ, Peacock WJ, Dennis ES (1996) Reduced DNA methylation in Arabidopsis thaliana results in abnormal plant development. Proc Natl Acad Sci USA 93:8449–8454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzgerald MS, McKnight TD, Shippen DE (1996) Characterization and developmental patterns of telomerase expression in plants. Proc Natl Acad Sci USA 93:14422–14427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzgerald MS, Riha K, Gao F, Ren S, McKnight TD, Shippen DE (1999) Disruption of the telomerase catalytic subunit gene from Arabidopsis inactivates telomerase and leads to a slow loss of telomeric DNA. Proc Natl Acad Sci USA 96:14813–14818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulcher N, Sablowski R (2009) Hypersensitivity to DNA damage in plant stem cell niches. Proc Natl Acad Sci USA 106:20984–20988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Cao M, O’Sullivan R, Peters AH, Jenuwein T, Blasco MA (2004) Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet 36:94–99

    Article  CAS  PubMed  Google Scholar 

  • Gendrel AV, Lippman Z, Yordan C, Colot V, Martienssen RA (2002) Dependence of heterochromatic histone H3 methylation patterns on the Arabidopsis gene DDM1. Science 297:1871–1873

    Article  CAS  PubMed  Google Scholar 

  • Gohring J, Fulcher N, Jacak J, Riha K (2014) TeloTool: a new tool for telomere length measurement from terminal restriction fragment analysis with improved probe intensity correction. Nucleic Acids Res 42:e21

    Article  PubMed  Google Scholar 

  • Gonzalo S, Jaco I, Fraga MF, Chen T, Li E, Esteller M, Blasco MA (2006) DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol 8:416–424

    Article  CAS  PubMed  Google Scholar 

  • Hashimura Y, Ueguchi C (2011) The Arabidopsis MERISTEM DISORGANIZATION 1 gene is required for the maintenance of stem cells through the reduction of DNA damage. Plant J 68:657–669

    Article  CAS  PubMed  Google Scholar 

  • Heacock M, Spangler E, Riha K, Puizina J, Shippen DE (2004) Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining. EMBO J 23:2304–2313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heacock ML, Idol RA, Friesner JD, Britt AB, Shippen DE (2007) Telomere dynamics and fusion of critically shortened telomeres in plants lacking DNA ligase IV. Nucleic Acids Res 35:6490–6500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemann MT, Strong MA, Hao LY, Greider CW (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107:67–77

    Article  CAS  PubMed  Google Scholar 

  • Hirochika H, Okamoto H, Kakutani T (2000) Silencing of retrotransposons in arabidopsis and reactivation by the ddm1 mutation. Plant Cell 12:357–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain D, Cooper JP (2010) Telomeric strategies: means to an end. Annu Rev Genet 44:243–269

    Article  CAS  PubMed  Google Scholar 

  • Jeddeloh JA, Stokes TL, Richards EJ (1999) Maintenance of genomic methylation requires a SWI2/SNF2-like protein. Nat Genet 22:94–97

    Article  CAS  PubMed  Google Scholar 

  • Kakutani T, Jeddeloh JA, Flowers SK, Munakata K, Richards EJ (1996) Developmental abnormalities and epimutations associated with DNA hypomethylation mutations. Proc Natl Acad Sci USA 93:12406–12411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kannan K, Nelson AD, Shippen DE (2008) Dyskerin is a component of the Arabidopsis telomerase RNP required for telomere maintenance. Mol Cell Biol 28:2332–2341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kazda A, Zellinger B, Rossler M, Derboven E, Kusenda B, Riha K (2012) Chromosome end protection by blunt-ended telomeres. Genes Dev 26:1703–1713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lazzerini-Denchi E, Sfeir A (2016) Stop pulling my strings—what telomeres taught us about the DNA damage response. Nat Rev Mol Cell Biol 17:364–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JR, Xie X, Yang K, Zhang J, Lee SY, Shippen DE (2016). Dynamic interactions of Arabidopsis TEN1: stabilizing telomeres in response to heat stress. Plant Cell

  • Leehy KA, Lee JR, Song X, Renfrew KB, Shippen DE (2013) MERISTEM DISORGANIZATION1 encodes TEN1, an essential telomere protein that modulates telomerase processivity in Arabidopsis. Plant Cell 25:1343–1354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lendvay TS, Morris DK, Sah J, Balasubramanian B, Lundblad V (1996). Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics 144:1399–1412

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li B, Lustig AJ (1996) A novel mechanism for telomere size control in Saccharomyces cerevisiae. Genes Dev 10:1310–1326

    Article  CAS  PubMed  Google Scholar 

  • Li B, Jog SP, Reddy S, Comai L (2008) WRN controls formation of extrachromosomal telomeric circles and is required for TRF2∆B-mediated telomere shortening. Mol Cell Biol 28:1892–1904

    Article  PubMed  PubMed Central  Google Scholar 

  • Lippman Z, Gendrel AV, Black M, Vaughn MW, Dedhia N, McCombie WR, Lavine K, Mittal V, May B, Kasschau KD et al (2004) Role of transposable elements in heterochromatin and epigenetic control. Nature 430:471–476

    Article  CAS  PubMed  Google Scholar 

  • Longhese MP (2008) DNA damage response at functional and dysfunctional telomeres. Genes Dev 22:125–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lustig AJ (2003) Clues to catastrophic telomere loss in mammals from yeast telomere rapid deletion. Nat Rev Genet 4:916–923

    Article  CAS  PubMed  Google Scholar 

  • Martinez P, Blasco MA (2015) Replicating through telomeres: a means to an end. Trends Biochem Sci 40:504–515

    Article  CAS  PubMed  Google Scholar 

  • McEachern MJ, Blackburn EH (1995) Runaway telomere elongation caused by telomerase RNA gene mutations. Nature 376:403–409

    Article  CAS  PubMed  Google Scholar 

  • Miura A, Yonebayashi S, Watanabe K, Toyama T, Shimada H, Kakutani T (2001) Mobilization of transposons by a mutation abolishing full DNA methylation in Arabidopsis. Nature 411:212–214

    Article  CAS  PubMed  Google Scholar 

  • Nelson AD, Shippen DE (2012) Surprises from the chromosome front: lessons from Arabidopsis on telomeres and telomerase. Cold Spring Harb Symp Quant Biol 77:7–15

    Article  CAS  PubMed  Google Scholar 

  • O’Sullivan RJ, Karlseder J (2010) Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol 11:171–181

    Article  PubMed  PubMed Central  Google Scholar 

  • Ogrocka A, Polanska P, Majerova E, Janeba Z, Fajkus J, Fojtova M (2014) Compromised telomere maintenance in hypomethylated Arabidopsis thaliana plants. Nucleic Acids Res 42:2919–2931

    Article  CAS  PubMed  Google Scholar 

  • Ottaviani A, Gilson E, Magdinier F (2008) Telomeric position effect: from the yeast paradigm to human pathologies? Biochimie 90:93–107

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffer V, Lingner J (2012) TERRA promotes telomere shortening through exonuclease 1-mediated resection of chromosome ends. PLoS Genet 8:e1002747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Probst AV, Fransz PF, Paszkowski J, Scheid MO (2003) Two means of transcriptional reactivation within heterochromatin. Plant J 33:743–749

    Article  CAS  PubMed  Google Scholar 

  • Questa JI, Fina JP, Casati P (2013) DDM1 and ROS1 have a role in UV-B induced- and oxidative DNA damage in A. thaliana. Front Plant Sci 4:420

    Article  PubMed  PubMed Central  Google Scholar 

  • Renfrew KB, Song X, Lee JR, Arora A, Shippen DE (2014) POT1a and components of CST engage telomerase and regulate its activity in Arabidopsis. PLoS Genet 10:e1004738

    Article  PubMed  PubMed Central  Google Scholar 

  • Richards EJ, Ausubel FM (1988) Isolation of a higher eukaryotic telomere from Arabidopsis thaliana. Cell 53:127–136

    Article  CAS  PubMed  Google Scholar 

  • Riha K, Shippen DE (2003) Ku is required for telomeric C-rich strand maintenance but not for end-to-end chromosome fusions in Arabidopsis. Proc Natl Acad Sci USA 100:611–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riha K, McKnight TD, Griffing LR, Shippen DE (2001) Living with genome instability: plant responses to telomere dysfunction. Science 291:1797–1800

    Article  CAS  PubMed  Google Scholar 

  • Riha K, Watson JM, Parkey J, Shippen DE (2002) Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70. EMBO J 21:2819–2826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ronemus MJ, Galbiati M, Ticknor C, Chen J, Dellaporta SL (1996) Demethylation-induced developmental pleiotropy in Arabidopsis. Science 273:654–657

    Article  CAS  PubMed  Google Scholar 

  • Sandell LL, Zakian VA (1993) Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 75:729–739

    Article  CAS  PubMed  Google Scholar 

  • Shaked H, Avivi-Ragolsky N, Levy AA (2006) Involvement of the Arabidopsis SWI2/SNF2 chromatin remodeling gene family in DNA damage response and recombination. Genetics 173:985–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shakirov EV, Shippen DE (2004) Length regulation and dynamics of individual telomere tracts in wild-type Arabidopsis. Plant Cell 16:1959–1967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slagboom PE, Droog S, Boomsma DI (1994) Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet 55:876–882

    CAS  PubMed  PubMed Central  Google Scholar 

  • Song X, Leehy K, Warrington RT, Lamb JC, Surovtseva YV, Shippen DE (2008) STN1 protects chromosome ends in Arabidopsis thaliana. Proc Natl Acad Sci USA 105:19815–19820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stansel RM, de Lange T, Griffith JD (2001) T-loop assembly in vitro involves binding of TRF2 near the 3′ telomeric overhang. EMBO J 20:5532–5540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Surovtseva YV, Shakirov EV, Vespa L, Osbun N, Song X, Shippen DE (2007) Arabidopsis POT1 associates with the telomerase RNP and is required for telomere maintenance. EMBO J 26:3653–3661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Surovtseva YV, Churikov D, Boltz KA, Song X, Lamb JC, Warrington R, Leehy K, Heacock M, Price CM, Shippen DE (2009) Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Mol Cell 36:207–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsukahara S, Kobayashi A, Kawabe A, Mathieu O, Miura A, Kakutani T (2009) Bursts of retrotransposition reproduced in Arabidopsis. Nature 461:423–426

    Article  CAS  PubMed  Google Scholar 

  • Vaquero-Sedas MI, Vega-Palas MA (2014) Determination of Arabidopsis thaliana telomere length by PCR. Sci Rep 4:5540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaquero-Sedas MI, Gamez-Arjona FM, Vega-Palas MA (2011) Arabidopsis thaliana telomeres exhibit euchromatic features. Nucleic Acids Res 39:2007–2017

    Article  CAS  PubMed  Google Scholar 

  • Vaquero-Sedas MI, Luo C, Vega-Palas MA (2012) Analysis of the epigenetic status of telomeres by using ChIP-seq data. Nucleic Acids Res 40:e163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vega-Vaquero A, Bonora G, Morselli M, Vaquero-Sedas MI, Rubbi L, Pellegrini M, Vega-Palas MA (2016) Novel features of telomere biology revealed by the absence of telomeric DNA methylation. Genome Res 26:1047–1056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vicient CM (2010) Transcriptional activity of transposable elements in maize. BMC Genom 11:601

    Article  Google Scholar 

  • Vongs A, Kakutani T, Martienssen RA, Richards EJ (1993) Arabidopsis thaliana DNA methylation mutants. Science 260:1926–1928

    Article  CAS  PubMed  Google Scholar 

  • Vrbsky J, Akimcheva S, Watson JM, Turner TL, Daxinger L, Vyskot B, Aufsatz W, Riha K (2010) siRNA-mediated methylation of Arabidopsis telomeres. PLoS Genet 6:e1000986

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang RC, Smogorzewska A, de Lange T (2004) Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119:355–368

    Article  CAS  PubMed  Google Scholar 

  • Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239:197–201

    Article  CAS  PubMed  Google Scholar 

  • Watson JM, Riha K (2010) Comparative biology of telomeres: where plants stand. FEBS Lett 584:3752–3759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watson JM, Bulankova P, Riha K, Shippen DE, Vyskot B (2005) Telomerase-independent cell survival in Arabidopsis thaliana. Plant J 43:662–674

    Article  CAS  PubMed  Google Scholar 

  • Zellinger B, Akimcheva S, Puizina J, Schirato M, Riha K (2007) Ku suppresses formation of telomeric circles and alternative telomere lengthening in Arabidopsis. Mol Cell 27:163–169

    Article  CAS  PubMed  Google Scholar 

  • Zemach A, Kim MY, Hsieh PH, Coleman-Derr D, Eshed-Williams L, Thao K, Harmer SL, Zilberman D (2013) The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell 153:193–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Jacobsen SE (2006) Genetic analyses of DNA methyltransferases in Arabidopsis thaliana. Cold Spring Harb Symp Quant Biol 71:439–447

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Yazaki J, Sundaresan A, Cokus S, Chan SW, Chen H, Henderson IR, Shinn P, Pellegrini M, Jacobsen SE et al (2006) Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell 126:1189–1201

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Li Y, Xu T, Srivastava AK, Wang D, Zeng L, Yang L, He L, Zhang H, Zheng Z et al (2016) The chromatin remodeler DDM1 promotes hybrid vigor by regulating salicylic acid metabolism. Cell Discov 2:16027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Keith Slotkin for providing mutant seeds, Lanying Zeng for sharing her fluorescence microscope, members of the Shippen lab for insightful comments and Jeff Kapler and Eugene Shakirov for critically reading the manuscript. This work was supported by the National Institutes of Health (GM065383 to D.E.S.).

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  1. Department of Biochemistry and Biophysics, Texas A&M University, 2128 TAMU, College Station, TX, 77843-2128, USA

    Xiaoyuan Xie & Dorothy E. Shippen

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  1. Xiaoyuan Xie
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Correspondence to Dorothy E. Shippen.

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Xie, X., Shippen, D.E. DDM1 guards against telomere truncation in Arabidopsis. Plant Cell Rep 37, 501–513 (2018). https://doi.org/10.1007/s00299-017-2245-6

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