Role of transposable elements in heterochromatin and epigenetic control

Abstract

Heterochromatin has been defined as deeply staining chromosomal material that remains condensed in interphase, whereas euchromatin undergoes de-condensation1. Heterochromatin is found near centromeres and telomeres, but interstitial sites of heterochromatin (knobs) are common in plant genomes and were first described in maize2. These regions are repetitive and late-replicating3. In Drosophila, heterochromatin influences gene expression, a heterochromatin phenomenon called position effect variegation4. Similarities between position effect variegation in Drosophila and gene silencing in maize mediated by “controlling elements” (that is, transposable elements) led in part to the proposal that heterochromatin is composed of transposable elements, and that such elements scattered throughout the genome might regulate development2. Using microarray analysis, we show that heterochromatin in Arabidopsis is determined by transposable elements and related tandem repeats, under the control of the chromatin remodelling ATPase DDM1 (Decrease in DNA Methylation 1). Small interfering RNAs (siRNAs) correspond to these sequences, suggesting a role in guiding DDM1. We also show that transposable elements can regulate genes epigenetically, but only when inserted within or very close to them. This probably accounts for the regulation by DDM1 and the DNA methyltransferase MET1 of the euchromatic, imprinted gene FWA, as its promoter is provided by transposable-element-derived tandem repeats that are associated with siRNAs.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The heterochromatic knob (hk4S) on chromosome 4.
Figure 2: Expression and chromatin profiling of wild type and ddm1 using genomic tiling microarrays.
Figure 3: Cluster analysis.
Figure 4: DDM1-dependent gene regulation.

References

  1. 1

    Heitz, E. Das heterochromatin der Moose. Jehrb. Wiss. Botanik 69, 762–818 (1928)

    Google Scholar 

  2. 2

    McClintock, B. Chromosome organization and genic expression. Cold Spring Harb. Symp. Quant. Biol. 16, 13–47 (1951)

    CAS  Article  Google Scholar 

  3. 3

    Hennig, W. Heterochromatin. Chromosoma 108, 1–9 (1999)

    CAS  Article  Google Scholar 

  4. 4

    Schotta, G., Ebert, A., Dorn, R. & Reuter, G. Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Semin. Cell Dev. Biol. 14, 67–75 (2003)

    CAS  Article  Google Scholar 

  5. 5

    Fransz, P., De Jong, J. H., Lysak, M., Castiglione, M. R. & Schubert, I. Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate. Proc. Natl Acad. Sci. USA 99, 14584–14589 (2002)

    ADS  CAS  Article  Google Scholar 

  6. 6

    CSHL/WUGSC/PEB, Arabidopsis Sequencing Consortium. The complete sequence of a heterochromatic island from a higher eukaryote. Cell 100, 377–386 (2000)

    Article  Google Scholar 

  7. 7

    Arabidopsis Genome Initiative, Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796–815 (2000)

    ADS  Article  Google Scholar 

  8. 8

    Jurka, J. Repbase update: a database and an electronic journal of repetitive elements. Trends Genet. 16, 418–420 (2000)

    CAS  Article  Google Scholar 

  9. 9

    Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001)

    CAS  Article  Google Scholar 

  10. 10

    Vermaak, D., Ahmad, K. & Henikoff, S. Maintenance of chromatin states: an open-and-shut case. Curr. Opin. Cell Biol. 15, 266–274 (2003)

    CAS  Article  Google Scholar 

  11. 11

    Martienssen, R. A. & Colot, V. DNA methylation and epigenetic inheritance in plants and filamentous fungi. Science 293, 1070–1074 (2001)

    CAS  Article  Google Scholar 

  12. 12

    Lippman, Z., May, B., Yordan, C., Singer, T. & Martienssen, R. Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification. PLoS Biol. 1, E67 (2003)

    Article  Google Scholar 

  13. 13

    Verbsky, M. L. & Richards, E. J. Chromatin remodeling in plants. Curr. Opin. Plant Biol. 4, 494–500 (2001)

    CAS  Article  Google Scholar 

  14. 14

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

    ADS  CAS  Article  Google Scholar 

  15. 15

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

    CAS  Article  Google Scholar 

  16. 16

    Sijen, T. & Plasterk, R. H. Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature 426, 310–314 (2003)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Aravin, A. A. et al. Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr. Biol. 11, 1017–1027 (2001)

    CAS  Article  Google Scholar 

  18. 18

    Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002)

    ADS  CAS  Article  Google Scholar 

  19. 19

    Martienssen, R. A. Maintenance of heterochromatin by RNA interference of tandem repeats. Nature Genet. 35, 213–214 (2003)

    CAS  Article  Google Scholar 

  20. 20

    Barkan, A. & Martienssen, R. A. Inactivation of maize transposon Mu suppresses a mutant phenotype by activating an outward-reading promoter near the end of Mu1. Proc. Natl Acad. Sci. USA 88, 3502–3506 (1991)

    ADS  CAS  Article  Google Scholar 

  21. 21

    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  Article  Google Scholar 

  22. 22

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

    ADS  CAS  Article  Google Scholar 

  23. 23

    Nagaki, K. et al. Sequencing of a rice centromere uncovers active genes. Nature Genet. 36, 138–145 (2004)

    CAS  Article  Google Scholar 

  24. 24

    Rabinowicz, P. D. et al. Genes and transposons are differentially methylated in plants, but not in mammals. Genome Res. 13, 2658–2664 (2003)

    CAS  Article  Google Scholar 

  25. 25

    Pal-Bhadra, M. et al. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303, 669–672 (2004)

    ADS  CAS  Article  Google Scholar 

  26. 26

    Schramke, V. & Allshire, R. Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301, 1069–1074 (2003)

    ADS  CAS  Article  Google Scholar 

  27. 27

    Verdel, A. et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303, 672–676 (2004)

    ADS  CAS  Article  Google Scholar 

  28. 28

    Zilberman, D., Cao, X. & Jacobsen, S. E. ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 299, 716–719 (2003)

    ADS  CAS  Article  Google Scholar 

  29. 29

    Seitz, H. et al. Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nature Genet. 34, 261–262 (2003)

    ADS  CAS  Article  Google Scholar 

  30. 30

    Chan, S. W. et al. RNA silencing genes control de novo DNA methylation. Science 303, 1336 (2004)

    CAS  Article  Google Scholar 

  31. 31

    Xie, Z. et al. Genetic and functional diversification of small RNA pathways in plants. PLoS Biol. 2, E104 (2004)

    Article  Google Scholar 

  32. 32

    Craig, B. A., Black, M. A. & Doerge, R. W. Gene expression data: the technology and statistical analysis. J. Agric. Biol. Environ. Stat. 8, 1–28 (2003)

    Article  Google Scholar 

Download references

Acknowledgements

We thank E. Richards and our colleagues T. Osborn, L. Comai, J. Chen and J. Birchler for their comments and advice. We also thank P. Rabinowicz for advice on ChIP microarray experiments. V.C. thanks M. Caboche for laboratory space and continuous support. Z.L. is an Arnold and Mabel Beckman graduate fellow in the Watson School of Biological Sciences. A.V.G. is supported by a graduate studentship from the French Ministry of Research. M.V. is a National Science Foundation Bioinformatics postdoctoral fellow. This work was supported by a grant from the NSF Plant Genome Program (to R.W.D. and R.M.), as well as grants from Genopole and the CNRS (to V.C.), grants from NSF and NIH to J. C., and NIH to R.M.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Vincent Colot or Rob Martienssen.

Ethics declarations

Competing interests

R. Martienssen and W. R. McCombie have financial interests in Orion Genomics LLC, a biotechnology company that has commercialized the DNA methylation profiling method under the trademark MethylScope.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lippman, Z., Gendrel, A., Black, M. et al. Role of transposable elements in heterochromatin and epigenetic control. Nature 430, 471–476 (2004). https://doi.org/10.1038/nature02651

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing