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Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription

Abstract

Cytosine methylation, a common form of DNA modification that antagonizes transcription, is found at transposons and repeats in vertebrates, plants and fungi. Here we have mapped DNA methylation in the entire Arabidopsis thaliana genome at high resolution. DNA methylation covers transposons and is present within a large fraction of A. thaliana genes. Methylation within genes is conspicuously biased away from gene ends, suggesting a dependence on RNA polymerase transit. Genic methylation is strongly influenced by transcription: moderately transcribed genes are most likely to be methylated, whereas genes at either extreme are least likely. In turn, transcription is influenced by methylation: short methylated genes are poorly expressed, and loss of methylation in the body of a gene leads to enhanced transcription. Our results indicate that genic transcription and DNA methylation are closely interwoven processes.

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Figure 1: Genome-wide mapping of DNA methylation in A. thaliana.
Figure 2: Distribution of methylated genes and transposable elements along chromosome arms.
Figure 3: Functional annotation of methylated (M) and unmethylated (U) genes.
Figure 4: Analysis of the distribution of DNA methylation within the A. thaliana genome.
Figure 5: Relationship between DNA methylation and transcription.
Figure 6: Correspondence between RNA polymerase II (Pol II) and DNA methylation.
Figure 7: Analysis of expression in met1-6 mutant plants.
Figure 8: Model for transcription-coupled DNA methylation.

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References

  1. 1

    Chan, S.W., Henderson, I.R. & Jacobsen, S.E. Gardening the genome: DNA methylation in Arabidopsis thaliana. Nat. Rev. Genet. 6, 351–360 (2005).

    CAS  Google Scholar 

  2. 2

    Freitag, M. & Selker, E.U. Controlling DNA methylation: many roads to one modification. Curr. Opin. Genet. Dev. 15, 191–199 (2005).

    CAS  PubMed  Google Scholar 

  3. 3

    Goll, M.G. & Bestor, T.H. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74, 481–514 (2005).

    CAS  PubMed  Google Scholar 

  4. 4

    Klose, R.J. & Bird, A.P. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31, 89–97 (2006).

    CAS  PubMed  Google Scholar 

  5. 5

    Kakutani, T., Kato, M., Kinoshita, T. & Miura, A. Control of development and transposon movement by DNA methylation in Arabidopsis thaliana. Cold Spring Harb. Symp. Quant. Biol. 69, 139–143 (2004).

    CAS  PubMed  Google Scholar 

  6. 6

    Kato, M., Miura, A., Bender, J., Jacobsen, S.E. & Kakutani, T. Role of CG and non-CG methylation in immobilization of transposons in Arabidopsis. Curr. Biol. 13, 421–426 (2003).

    CAS  PubMed  Google Scholar 

  7. 7

    Selker, E.U. Genome defense and DNA methylation in Neurospora. Cold Spring Harb. Symp. Quant. Biol. 69, 119–124 (2004).

    CAS  PubMed  Google Scholar 

  8. 8

    Singer, T., Yordan, C. & Martienssen, R.A. Robertson' Mutator transposons in A. thaliana are regulated by the chromatin-remodeling gene decrease in DNA methylation (DDM1). Genes Dev. 15, 591–602 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Bestor, T.H. DNA methylation: evolution of a bacterial immune function into a regulator of gene expression and genome structure in higher eukaryotes. Phil. Trans. R. Soc. Lond. B 326, 179–187 (1990).

    CAS  Google Scholar 

  10. 10

    Bird, A.P. Gene number, noise reduction and biological complexity. Trends Genet. 11, 94–100 (1995).

    CAS  Google Scholar 

  11. 11

    Field, L.M., Lyko, F., Mandrioli, M. & Prantera, G. DNA methylation in insects. Insect Mol. Biol. 13, 109–115 (2004).

    CAS  PubMed  Google Scholar 

  12. 12

    Simmen, M.W. et al. Nonmethylated transposable elements and methylated genes in a chordate genome. Science 283, 1164–1167 (1999).

    CAS  PubMed  Google Scholar 

  13. 13

    Tran, R.K. et al. DNA methylation profiling identifies CG methylation clusters in Arabidopsis genes. Curr. Biol. 15, 154–159 (2005).

    CAS  Google Scholar 

  14. 14

    Xiao, W. et al. Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1 methyltransferase and DME glycosylase. Dev. Cell 5, 891–901 (2003).

    CAS  PubMed  Google Scholar 

  15. 15

    Weber, M. et al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat. Genet. 37, 853–862 (2005).

    CAS  Google Scholar 

  16. 16

    Jurka, J. et al. Repbase Update, a database of eukaryotic repetitive elements. Cytogenet. Genome Res. 110, 462–467 (2005).

    CAS  Google Scholar 

  17. 17

    Kato, M., Takashima, K. & Kakutani, T. Epigenetic control of CACTA transposon mobility in Arabidopsis thaliana. Genetics 168, 961–969 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Berardini, T.Z. et al. Functional annotation of the Arabidopsis genome using controlled vocabularies. Plant Physiol. 135, 745–755 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Lippman, Z. et al. Role of transposable elements in heterochromatin and epigenetic control. Nature 430, 471–476 (2004).

    CAS  PubMed  Google Scholar 

  20. 20

    Tran, R.K. et al. Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis. Genome Biol. 6, R90 (2005).

    PubMed  PubMed Central  Google Scholar 

  21. 21

    Zilberman, D. & Henikoff, S. Silencing of transposons in plant genomes: kick them when they're down. Genome Biol. 5, 249 (2004).

    PubMed  PubMed Central  Google Scholar 

  22. 22

    Soppe, W.J. et al. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene. Mol. Cell 6, 791–802 (2000).

    CAS  Google Scholar 

  23. 23

    Kinoshita, T. et al. One-way control of FWA imprinting in Arabidopsis endosperm by DNA methylation. Science 303, 521–523 (2004).

    CAS  PubMed  Google Scholar 

  24. 24

    Jullien, P.E., Kinoshita, T., Ohad, N. & Berger, F. Maintenance of DNA methylation during the Arabidopsis life cycle is essential for parental imprinting. Plant Cell 18, 1360–1372 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Gehring, M. et al. DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation. Cell 124, 495–506 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Schmid, M. et al. A gene expression map of Arabidopsis thaliana development. Nat. Genet. 37, 501–506 (2005).

    CAS  PubMed  Google Scholar 

  27. 27

    Zhang, X. et al. Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell 126, 1189–1201 (2006).

    CAS  PubMed  Google Scholar 

  28. 28

    Gilfillan, G.D. et al. Chromosome-wide gene-specific targeting of the Drosophila dosage compensation complex. Genes Dev. 20, 858–870 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Barry, C., Faugeron, G. & Rossignol, J.L. Methylation induced premeiotically in Ascobolus: coextension with DNA repeat lengths and effect on transcript elongation. Proc. Natl. Acad. Sci. USA 90, 4557–4561 (1993).

    CAS  PubMed  Google Scholar 

  30. 30

    Rountree, M.R. & Selker, E.U. DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa. Genes Dev. 11, 2383–2395 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Hohn, T., Corsten, S., Rieke, S., Muller, M. & Rothnie, H. Methylation of coding region alone inhibits gene expression in plant protoplasts. Proc. Natl. Acad. Sci. USA 93, 8334–8339 (1996).

    CAS  PubMed  Google Scholar 

  32. 32

    Lorincz, M.C., Dickerson, D.R., Schmitt, M. & Groudine, M. Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat. Struct. Mol. Biol. 11, 1068–1075 (2004).

    CAS  Google Scholar 

  33. 33

    Belotserkovskaya, R., Saunders, A., Lis, J.T. & Reinberg, D. Transcription through chromatin: understanding a complex FACT. Biochim. Biophys. Acta 1677, 87–99 (2004).

    CAS  PubMed  Google Scholar 

  34. 34

    Kaplan, C.D., Laprade, L. & Winston, F. Transcription elongation factors repress transcription initiation from cryptic sites. Science 301, 1096–1099 (2003).

    CAS  PubMed  Google Scholar 

  35. 35

    Mason, P.B. & Struhl, K. The FACT complex travels with elongating RNA polymerase II and is important for the fidelity of transcriptional initiation in vivo. Mol. Cell. Biol. 23, 8323–8333 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Schwabish, M.A. & Struhl, K. Asf1 mediates histone eviction and deposition during elongation by RNA polymerase II. Mol. Cell 22, 415–422 (2006).

    CAS  PubMed  Google Scholar 

  37. 37

    Johnson, L., Cao, X. & Jacobsen, S. Interplay between two epigenetic marks. DNA methylation and histone H3 lysine 9 methylation. Curr. Biol. 12, 1360–1367 (2002).

    CAS  PubMed  Google Scholar 

  38. 38

    Svejstrup, J.Q. Transcription: histones face the FACT. Science 301, 1053–1055 (2003).

    CAS  PubMed  Google Scholar 

  39. 39

    Thibaud-Nissen, F. et al. Development of Arabidopsis whole-genome microarrays and their application to the discovery of binding sites for the TGA2 transcription factor in salicylic acid-treated plants. Plant J. 47, 152–162 (2006).

    CAS  PubMed  Google Scholar 

  40. 40

    Liu, C.L., Schreiber, S.L. & Bernstein, B.E. Development and validation of a T7 based linear amplification for genomic DNA. BMC Genomics 4, 19 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Jacobsen, S.E., Sakai, H., Finnegan, E.J., Cao, X. & Meyerowitz, E.M. Ectopic hypermethylation of flower-specific genes in Arabidopsis. Curr. Biol. 10, 179–186 (2000).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank J. Penterman (University of California Berkeley) for providing genomic DNA, R.L. Fischer (University of California Berkeley) for met1-6 seeds, M.E. Figueroa and J. Greally for help with the linear amplification protocol, T.D. Bryson for technical assistance and P. Talbert for comments on the manuscript. D.Z. is a Leukemia and Lymphoma Society Fellow. M.G. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation.

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This study was designed by D.Z. and S.H.; D.Z., M.G. and R.K.T. performed the experiments; D.Z., T.B. and S.H. analyzed the data and D.Z. and S.H. wrote the paper.

Corresponding author

Correspondence to Steven Henikoff.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Bisulfite sequencing analysis of Arabidopsis genes. (PDF 274 kb)

Supplementary Fig. 2

Functional annotation of methylated and unmethylated genes. (PDF 437 kb)

Supplementary Fig. 3

Box plots of genic methylation. (PDF 406 kb)

Supplementary Fig. 4

Relationship between DNA methylation and expression in Arabidopsis. (PDF 1189 kb)

Supplementary Table 1

Bisulfite sequencing data, methylated vs. unmethylated gene calls and correlation between methylation in wild-type and expression in met1-6. (XLS 1352 kb)

Supplementary Table 2

Average transcription levels and lengths of genes in functional categories. (PDF 12 kb)

Supplementary Table 3

Methylated genes are preferentially targeted by siRNAs. (PDF 8 kb)

Supplementary Note (PDF 1154 kb)

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Zilberman, D., Gehring, M., Tran, R. et al. Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription. Nat Genet 39, 61–69 (2007). https://doi.org/10.1038/ng1929

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