Skip to main content
SpringerLink
Log in

Methylation-Based Markers

  • Chapter
  • First Online:
Diagnostics in Plant Breeding

  • 2838 Accesses

Abstract

DNA methylation is due to the addition of a methyl group in the cyclic carbon-5 of cytosine. This modification can have important phenotypic consequences and be inherited through the transmission of epigenetic alleles (epialleles) over many generations. These heritable epigenetic alleles can be considered as a source of polymorphism and could be a source of variation for selection. A biomarker is a substance or a process that is indicative of a phenotype or a biological event and plant breeding would benefit very much of biomarkers constituted by polymorphisms associated to epialleles. Several methodologies to study epigenetic modifications related to DNA methylation have been developed and noticeably expanded in the recent years. Here, we present a series of techniques and some examples of their use to study epigenetic variation in plants and to develop biomarkers useful in plant breeding programs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams RLP (1996) DNA methylation. In: Bittar EE (ed) Principles of medical biology, vol 5. JAI Press Inc, New York, pp 33–66

    Google Scholar 

  • Ashikawa I (2001) Surveying CpG methylation at 5-CCGG in the genomes of rice cultivars. Plant Mol Biol 45:31–39

    Article  PubMed  CAS  Google Scholar 

  • Baek D, Jiang J, Chung JS, Wang B, Chen J, Xin Z, Shi H (2011) Regulated AtHKT1 gene expression by a distal enhancer element and DNA methylation in the promoter plays an important role in salt tolerance. Plant Cell Physiol 52:149–161

    Article  PubMed  CAS  Google Scholar 

  • Baubec T, Dinh HQ, Pecinka A, Rakic B, Rozhon W, Wohlrab B, Haeseler A, Scheida OM (2010) Cooperation of multiple chromatin modifications can generate unanticipated stability of epigenetic states in Arabidopsis. Plant Cell 22:34–47

    Article  PubMed  CAS  Google Scholar 

  • Bentley DR (2006) Whole-genome re-sequencing. Curr Opin Genet Dev 16:545–552

    Article  PubMed  CAS  Google Scholar 

  • Bibikova M, Lin Z, Zhou L, Chudin E, Garcia EW, Wu B, Doucet D, Thomas NJ, Wang Y, Vollmer E, Goldmann T, Seifart C, Jiang W, Barker DL, Chee MS, Floros J, Fan J (2006) High-throughput DNA methylation profiling using universal bead arrays. Genome Res 16:383–393

    Article  PubMed  CAS  Google Scholar 

  • Bird AP (1995) Gene number, noise reduction and biological complexity. Trends Genet 11:94–100

    Article  PubMed  CAS  Google Scholar 

  • Bird AP (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21

    Article  PubMed  CAS  Google Scholar 

  • Brandle JE, McHugh SG, James L, Labbe H, Miki BL (1995) Instability of transgene expression in field grown tobacco carrying the csr1-1 gene for sulfonylurea herbicide resistance. Biotechnology 13:994–998

    Article  CAS  Google Scholar 

  • Braslavsky I, Hebert B, Kartalov E, Quake SR (2003) Sequence information can be obtained from single DNA molecules. Proc Natl Acad Sci USA 100:3960–3964

    Article  PubMed  CAS  Google Scholar 

  • Cervera MT, Ruiz-Garcia L, Martinez-Zapater JM (2002) Analysis of DNA methylation in Arabidopsis thaliana based on methylation-sensitive AFLP markers. Mol Genet Genomics 268:543–552

    Article  PubMed  CAS  Google Scholar 

  • Clark SJ, Harrison J, Paul CL, Frommer M (1994) High sensitivity mapping of methylated cytosines. Nucleic Acids Res 22:2990–2997

    Article  PubMed  CAS  Google Scholar 

  • Cross SH, Charlton JA, Nan X, Bird AP (1994) Purification of CpG islands using a methylated DNA binding column. Nat Genet 6:236–244

    Article  PubMed  CAS  Google Scholar 

  • Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV, Laird PW (2000) MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res 28:E32

    Article  PubMed  CAS  Google Scholar 

  • Edwards JR, O’Donnell AH, Rollins RA, Peckham HE, Lee C, Milekic MH, Chanrion B, Fu Y, Su T, Hibshoosh H, Gingrich JA, Haghighi F, Nutter R, Bestor TH (2010) Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns. Genome Res 20:972–980

    Article  PubMed  CAS  Google Scholar 

  • Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, Peluso P, Rank D, Baybayan P, Bettman B, Bibillo A, Bjornson K, Chaudhuri B, Christians F, Cicero R, Clark S, Dalal R, Dewinter A, Dixon J, Foquet M, Gaertner A, Hardenbol P, Heiner C, Hester K, Holden D, Kearns G, Kong X, Kuse R, Lacroix Y, Lin S, Lundquist P, Ma C, Marks P, Maxham M, Murphy D, Park I, Pham T, Phillips M, Roy J, Sebra R, Shen G, Sorenson J, Tomaney A, Travers K, Trulson M, Vieceli J, Wegener J, Wu D, Yang A, Zaccarin D, Zhao P, Zhong F, Korlach J, Turner S (2009) Real-time DNA sequencing from single polymerase molecules. Science 323:133–138

    Article  PubMed  CAS  Google Scholar 

  • Fan JB, Gunderson KL, Bibikova M, Yeakley JM, Chen J, Wickham Garcia E, Lebruska LL, Laurent M, Shen R, Barker D (2006) Illumina universal bead arrays. Methods Enzymol 410:57–73

    Article  PubMed  CAS  Google Scholar 

  • Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC, Clark TA, Korlach J, Turner SW (2010) Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods 7:461–465

    Article  PubMed  CAS  Google Scholar 

  • Gentil M, Maury S (2007) Characterization of epigenetic biomarkers using new molecular approaches. In: Varshney RK, Tuberosa R (eds) Genomics-assisted crop improvement. Vol 1: genomics approaches and platforms. Springer, Dordrecht, pp 351–370

    Chapter  Google Scholar 

  • Gupta R, Nagarajan A, Wajapeyee N (2010) Advances in genome-wide DNA methylation analysis. Biotechniques 49:iii–xi

    Article  PubMed  CAS  Google Scholar 

  • Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826

    Article  PubMed  CAS  Google Scholar 

  • Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232

    Article  PubMed  CAS  Google Scholar 

  • Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP (2009) The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41:178–186

    Article  PubMed  CAS  Google Scholar 

  • Kakutani T (2002) Epi-alleles in plants: inheritance of epigenetic information over generations. Plant Cell Physiol 43:1106–1111

    Article  PubMed  CAS  Google Scholar 

  • Keshet I, Schlesinger Y, Farkash S, Rand E, Hecht M, Segal E, Pikarski E, Young RA, Niveleau A, Cedar H, Simon I (2006) Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet 38:149–153

    Article  PubMed  CAS  Google Scholar 

  • Keyte A, Percifield R, Liu B, Wendel JF (2006) Infraspecific DNA methylation polymorphism in cotton (Gossypium hirsutum L.). J Hered 97:445–446

    Article  Google Scholar 

  • Knox MR, Ellis THN (2001) Stability and inheritance of methylation states at PstI sites in Pisum. Mol Genet Genomics 265:497–507

    Article  PubMed  CAS  Google Scholar 

  • Koga Y, Pelizzola M, Cheng E, Krauthammer M, Sznol M, Ariyan S, Narayan D, Molinaro AM, Halaban R, Weissman SM (2009) Genome-wide screen of promoter methylation identifies novel markers in melanoma. Genome Res 19:1462–1470

    Article  PubMed  CAS  Google Scholar 

  • Korch C, Hagblom P (1986) In-vivo-modified gonococcal plasmid pJD1. A model system for analysis of restriction enzyme sensitivity to DNA modifications. Eur J Biochem 161:519–524

    Article  PubMed  CAS  Google Scholar 

  • Kreil DP, Russell RR, Russell S (2006) Microarray oligonucleotide probes. Methods Enzymol 410:73–98

    Article  PubMed  CAS  Google Scholar 

  • Levene MJ, Korlach J, Turner SW, Foquet M, Craighead HG, Webb WW (2003) Zero-mode waveguides for single-molecule analysis at high concentrations. Science 299:682–686

    Article  PubMed  CAS  Google Scholar 

  • Levi A, Thomas CE, Newman M, Reddy UK, Zhang X, Xu Y (2004) ISSR and AFLP markers differ among American watermelon cultivars with limited genetic diversity. J Am Soc Hortic Sci 129:553–558

    CAS  Google Scholar 

  • Lippman Z, Gendrel AV, Colot V, Martienssen R (2005) Profiling DNA methylation patterns using genomic tiling microarrays. Nat Methods 2:219–224

    Article  PubMed  CAS  Google Scholar 

  • Lister R, O’Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR (2008) Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell 133:523–536

    Article  PubMed  CAS  Google Scholar 

  • Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–322

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Morgan M, Hutchison K, Calhoun VD (2010) A study of the influence of sex on genome wide methylation. PLoS One 5:e10028

    Article  PubMed  Google Scholar 

  • Matzke MA, Matzke AJM (1996) Stable epigenetic states in differentiated plant cells: implications for somaclonal variation and gene silencing in transgenic plants. In: Russo VEA, Martienssen RA, Riggs AD (eds) Epigenetic mechanisms of gene regulation. Cold Spring Harbor Laboratory Press, New York, pp 377–392

    Google Scholar 

  • McClelland M, Nelson M, Raschke E (1994) Effect of site-specific modifi- cation on restriction endonucleases and DNA modification methyltransferases. Nucleic Acids Res 22:3640–3659

    Article  PubMed  CAS  Google Scholar 

  • Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein BE, Nusbaum C, Jaffe DB, Gnirke A, Jaenisch R, Lander ES (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454:766–770

    PubMed  CAS  Google Scholar 

  • Metzker ML (2010) Sequencing technologies-the next generation. Nat Rev Genet 11:31–46

    Article  PubMed  CAS  Google Scholar 

  • Meyers BC, Vu TH, Tej SS, Ghazal H, Matvienko M, Agrawal V, Ning J, Haudenschild CD (2004) Analysis of the transcriptional complexity of Arabidopsis thaliana by massively parallel signature sequencing. Nat Biotechnol 22:1006–1011

    Article  PubMed  CAS  Google Scholar 

  • Nimmakayala P, Vajja G, Gist RA, Tomason YR, Levi A, Reddy UK (2011) Effect of DNA methylation on molecular diversity of watermelon heirlooms and stability of methylation specific polymorphisms across the genealogies. Euphytica 177:79–89

    Article  CAS  Google Scholar 

  • Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522

    Article  PubMed  CAS  Google Scholar 

  • Oda M, Glass JL, Thompson RF, Mo Y, Olivier EN, Figueroa ME, Selzer RR, Richmond TA, Zhang X, Dannenberg L, Green RD, Melnick A, Hatchwell E, Bouhassira EE, Verma A, Suzuki M, Greally JM (2009) High-resolution genome-wide cytosine methylation profiling with simultaneous copy number analysis and optimization for limited cell numbers. Nucleic Acids Res 37:3829–3839

    Article  PubMed  CAS  Google Scholar 

  • Penterman J, Zilberman D, Huh JH, Ballinger T, Henikoff S, Fischer RL (2007) DNA demethylation in the Arabidopsis genome. Proc Natl Acad Sci USA 104:6752–6757

    Article  PubMed  CAS  Google Scholar 

  • Regev A, Lamb MJ, Jablonka E (1998) The role of DNA methylation in invertebrates: developmental regulation or genome defense? Mol Biol Evol 15:880–891

    Article  CAS  Google Scholar 

  • Reyna-Lopez GE, Simpson J, Ruiz-Herrera J (1997) Differences in DNA methylation patterns are detectable during the dimorphic transition of fungi by amplification of restriction polymorphisms. Mol Gen Genet 253:703–710

    Article  PubMed  CAS  Google Scholar 

  • Reynaud C, Bruno C, Boullanger P, Grange J, Barbesti S, Niveleau A (1992) Monitoring of urinary excretion of modified nucleosides in cancer patients using a set of six monoclonal antibodies. Cancer Lett 61:255–262

    Article  PubMed  CAS  Google Scholar 

  • Riddle NC, Richards EJ (2002) The control of natural variation in cytosine methylation in Arabidopsis. Genetics 162:355–363

    PubMed  CAS  Google Scholar 

  • Rollins RA, Haghighi F, Edwards JR, Das R, Zhang MQ, Ju J, Bestor TH (2006) Large-scale structure of genomic methylation patterns. Genome Res 16:157–163

    Article  PubMed  CAS  Google Scholar 

  • Ruike Y, Imanaka Y, Sato F, Shimizu K, Tsujimoto G (2010) Genome- wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing. BMC Genomics 11:137

    Article  PubMed  Google Scholar 

  • Ruzov A, Savitskaya E, Hackett JA, Reddington JP, Prokhortchouk A, Madej MJ, Chekanov N, Li M, Dunican DS, Prokhortchouk E, Pennings S, Meehan RR (2009) The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development. Development 136:729–738

    Article  PubMed  CAS  Google Scholar 

  • Sae-Eung C, Kanchanaketu T, Sangduen N, Hongtrakul V (2012) DNA methylation and genetic diversity analysis of genus Cycas in Thailand. Afr J Biot 11:743–751

    CAS  Google Scholar 

  • Sakthivel K, Girishkumar K, Ramkumar G, Shenoy VV, Kajjidoni T, Salimath PM (2010) Alterations in inheritance pattern and level of cytosine DNA methylation, and their relationship with heterosis in rice. Euphytica 175:303–314

    Article  CAS  Google Scholar 

  • Sano H, Kamada I, Youssefian S, Katsumi M, Wabilko H (1990) A single treatment of rice seedlings with 5-azacytidine induces heritable dwarfism and undermethylation of genomic DNA. Mol Gen Genet 220:441–447

    Article  CAS  Google Scholar 

  • Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, Wang MD, Zhang K, Mitra RD, Church GM (2005) Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309:1728–1732

    Article  PubMed  CAS  Google Scholar 

  • Steward N, Ito M, Yamachuchi Y, Koizumi N, Sano H (2002) Periodic DNA methylation in maize nucleosomes and demethylation by environmental stress. J Biol Chem 277:37741–37746

    Article  PubMed  CAS  Google Scholar 

  • Suhr ST, Chang EA, Rodriguez RM, Wang K, Ross PJ, Beyhan Z, Murthy S, Cibelli JB (2009) Telomere dynamics in human cells reprogrammed to pluripotency. PLoS One 4:e8124

    Article  PubMed  Google Scholar 

  • Tsaftaris AS, Polidoros AN (2000) DNA methylation and plant breeding. Plant Breed Rev 18:87–176

    CAS  Google Scholar 

  • Tsaftaris AS, Polidoros AN, Koumproglou R, Tani E, Kovacevic N, Abatzidou E (2005) Epigenetic mechanisms in plants and their implications in plant breeding. In: Tuberosa R, Phillips RL, Gale M (eds) Proceedings of the international congress “in the wake of the double helix: from the green revolution to the gene revolution”, Bologna, Italy, 27–31 May 2003. Avenue Media, Bologna, pp 157–171

    Google Scholar 

  • Vaucheret H, Beclin C, Elmayan T, Feuerbach F, Godon C, Morel JB, Mourrain P, Palauqui JC, Vernhettes S (1998) Transgene-induced gene silencing in plants. Plant J 16:651–659

    Article  PubMed  CAS  Google Scholar 

  • Verhoeven KJF, van Dijk PJ, Biere A (2010) Changes in genomic methylation patterns during the formation of triploid asexual dandelion lineages. Mol Ecol 19:315–324

    Article  PubMed  CAS  Google Scholar 

  • Vos P, Hogers R, Bleeker M, Reijans M, van de Lee T, Hornes M, Fijters A, Pot J, Peleman J, Kuiper M, Zabeau M (1995) AFLP: a new technique for DNA fingerprinting. Nucleic Acids Res 23:4407–4414

    Article  PubMed  CAS  Google Scholar 

  • Wang JL, Tian A, Madlung H, Lee S, Chen M (2004) Sto- chastic and epigenetic changes of gene expression in Arabidopsis polyploids. Genetics 167:1961–1973

    Article  PubMed  CAS  Google Scholar 

  • Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schubeler D (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37:853–862

    Article  PubMed  CAS  Google Scholar 

  • Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M, Schübeler D (2007) Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39:457–466

    Article  PubMed  CAS  Google Scholar 

  • Weising K, Nybom H, Wolf K, Kahl G (2005) DNA Fingerprinting in plants, 2nd edn. CRC Press, Taylor & Francis, Boca Raton, p 444

    Book  Google Scholar 

  • Wolffe AP, Matzke MA (1999) Epigenetics: regulation through repression. Science 286:481–486

    Article  PubMed  CAS  Google Scholar 

  • Xiong LZ, Xu CG, Saghai Maroof MA, Zhang Q (1999) Patterns of cytosin methylation in an elite rice hybrid and its parental lines, detected by a methylation- sensitive amplification polymorphism technique. Mol Gen Genet 261:439–446

    Article  PubMed  CAS  Google Scholar 

  • Yan H, Kikuchi S, Neumann P, Zhang W, Wu Y, Chen F, Jiang J (2010) Genome-wide mapping of cytosine methylation revealed dynamic DNA methylation patterns associated with genes and centromeres in rice. Plant J 63:353–365

    Article  CAS  Google Scholar 

  • Yi C, Zhang S, Liu X, Bui HTN, Hong Y (2010) Does epigenetic polymorphism contribute to phenotypic variances in Jatropha curcas L.? BMC Plant Biol 10:259

    Article  PubMed  Google Scholar 

  • Yoder JA, Walsh CP, Bestor TH (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13:335–340

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Shiu S, Cal A, Borevitz JO (2008) Global analysis of genetic, epigenetic and transcriptional polymorphisms in Arabidopsis thaliana using whole genome tiling arrays. PLoS Genet 4:3

    Article  Google Scholar 

  • Zhao Y, Yu S, Ye W, Wang H, Wang J, Fang B (2010) Study on DNA cytosine methylation of cotton (Gossypium hirsutum L.) genome and its implication for salt tolerance. Agric Sci China 9:783–791

    Article  CAS  Google Scholar 

  • Zilberman D, Henikoff S (2007) Genome-wide analysis of DNA methylation patterns. Development 134:3959–3965

    Article  PubMed  CAS  Google Scholar 

  • Zilberman D, Gehring M, Tran RK, Ballinger T, Henikoff S (2007) Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription. Nat Genet 39:61–69

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Applied Biology, University of Perugia, Borgo XX Giugno 74, 06121, Perugia, Italy

    Emidio Albertini & Gianpiero Marconi

Authors
  1. Emidio Albertini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gianpiero Marconi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emidio Albertini .

Editor information

Editors and Affiliations

  1. Dept. Agronomy, Iowa State University, Agronomy Hall 1204, Ames, 50011, Iowa, USA

    Thomas Lübberstedt

  2. ICRISAT, Centre of Excellence in Genomics (CEG), Patancheru, 502 324, Andra Pradesh, India

    Rajeev K. Varshney

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Albertini, E., Marconi, G. (2013). Methylation-Based Markers. In: Lübberstedt, T., Varshney, R. (eds) Diagnostics in Plant Breeding. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5687-8_12

Download citation

Publish with us

Policies and ethics

Search

Navigation