The conserved Polycomb repressive complex 2 (PRC2) generates trimethylation of histone 3 lysine 27 (H3K27me3)1,2, a modification associated with stable epigenetic silencing3,4. Much is known about PRC2-induced silencing but key questions remain concerning its nucleation and stability. Vernalization, the perception and memory of winter in plants, is a classic epigenetic process that, in Arabidopsis, involves PRC2-based silencing of the floral repressor FLC5,6. The slow dynamics of vernalization, taking place over weeks in the cold, generate a level of stable silencing of FLC in the subsequent warm that depends quantitatively on the length of the prior cold. These features make vernalization an ideal experimental system to investigate both the maintenance of epigenetic states and the switching between them. Here, using mathematical modelling, chromatin immunoprecipitation and an FLC:GUS reporter assay, we show that the quantitative nature of vernalization is generated by H3K27me3-mediated FLC silencing in the warm in a subpopulation of cells whose number depends on the length of the prior cold. During the cold, H3K27me3 levels progressively increase at a tightly localized nucleation region within FLC. At the end of the cold, numerical simulations predict that such a nucleation region is capable of switching the bistable epigenetic state of an individual locus, with the probability of overall FLC coverage by silencing H3K27me3 marks depending on the length of cold exposure. Thus, the model predicts a bistable pattern of FLC gene expression in individual cells, a prediction we verify using the FLC:GUS reporter system. Our proposed switching mechanism, involving the local nucleation of an opposing histone modification, is likely to be widely relevant in epigenetic reprogramming.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Hansen, K. H. et al. A model for transmission of the H3K27me3 epigenetic mark. Nature Cell Biol. 10, 1291–1300 (2008)
Margueron, R. et al. Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461, 762–767 (2009)
Turner, B. M. Defining an epigenetic code. Nature Cell Biol. 9, 2–6 (2007)
Margueron, R. & Reinberg, D. Chromatin structure and the inheritance of epigenetic information. Nature Rev. Genet. 11, 285–296 (2010)
Sheldon, C. C. et al. The FLF MADS box gene: a repressor of flowering in Arabidopsis regulated by vernalization and methylation. Plant Cell 11, 445–458 (1999)
Michaels, S. D. & Amasino, R. M. FLOWERING LOCUS C encodes a novel MADS domain protein that acts as a repressor of flowering. Plant Cell 11, 949–956 (1999)
Sung, S. & Amasino, R. M. Vernalization in Arabidopsis thaliana is mediated by the PHD finger protein VIN3. Nature 427, 159–164 (2004)
Greb, T. et al. The PHD finger protein VRN5 functions in the epigenetic silencing of Arabidopsis FLC . Curr. Biol. 17, 73–78 (2007)
De Lucia, F., Crevillen, P., Jones, A. M., Greb, T. & Dean, C. A. PHD-Polycomb repressive complex 2 triggers the epigenetic silencing of FLC during vernalization. Proc. Natl Acad. Sci. USA 105, 16831–16836 (2008)
Wood, C. C. et al. The Arabidopsis thaliana vernalization response requires a polycomb-like protein complex that also includes VERNALIZATION INSENSITIVE 3. Proc. Natl Acad. Sci. USA 103, 14631–14636 (2006)
Gendall, A. R., Levy, Y. Y., Wilson, A. & Dean, C. The VERNALIZATION 2 gene mediates the epigenetic regulation of vernalization in Arabidopsis . Cell 107, 525–535 (2001)
Finnegan, E. J. & Dennis, E. S. Vernalization-induced trimethylation of histone H3 lysine 27 at FLC is not maintained in mitotically quiescent cells. Curr. Biol. 17, 1978–1983 (2007)
Dodd, I. B., Micheelsen, M. A., Sneppen, K. & Thon, G. Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell 129, 813–822 (2007)
Salazar, J. D., Foreman, J., Carr, I. A., Rand, D. A. & Millar, A. J. Mathematical model of the epigenetic control of vernalisation in Arabidopsis thaliana . Acta Hort. (ISHS) 803, 187–192 (2008)
Sedighi, M. & Sengupta, A. M. Epigenetic chromatin silencing: bistability and front propagation. Phys. Biol. 4, 246–255 (2007)
David-Rus, D., Mukhopadhyay, S., Lebowitz, J. L. & Sengupta, A. M. Inheritance of epigenetic chromatin silencing. J. Theor. Biol. 258, 112–120 (2009)
Mukhopadhyay, S., Nagaraj, V. H. & Sengupta, A. M. Locus dependence in epigenetic chromatin silencing. Biosystems 102, 49–54 (2010)
Kelemen, J. Z., Ratna, P., Scherrer, S. & Becskei, A. Spatial epigenetic control of mono- and bistable gene expression. PLoS Biol. 8, e1000332 (2010)
Kaufman, P. D. & Rando, O. J. Chromatin as a potential carrier of heritable information. Curr. Opin. Cell Biol. 22, 284–290 (2010)
Deal, R. B., Henikoff, J. G. & Henikoff, S. Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones. Science 328, 1161–1164 (2010)
Reddy, G. V., Heisler, M. G., Ehrhardt, D. W. & Meyerowitz, E. M. Real-time lineage analysis reveals oriented cell divisions associated with morphogenesis at the shoot apex of Arabidopsis thaliana . Development 131, 4225–4237 (2004)
Grandjean, O. et al. In vivo analysis of cell division, cell growth, and differentiation at the shoot apical meristem in Arabidopsis . Plant Cell 16, 74–87 (2004)
Levy, Y. Y., Mesnage, S., Mylne, J. S., Gendall, A. R. & Dean, C. Multiple roles of Arabidopsis VRN1 in vernalization and flowering time control. Science 297, 243–246 (2002)
Bastow, R. et al. Vernalization requires epigenetic silencing of FLC by histone methylation. Nature 427, 164–167 (2004)
Sheldon, C. C. et al. Resetting of FLOWERING LOCUS C expression after epigenetic repression by vernalization. Proc. Natl Acad. Sci. USA 105, 2214–2219 (2008)
Burn, J. E., Bagnall, D. J., Metzger, J. D., Dennis, E. S. & Peacock, W. J. DNA methylation, vernalization, and the initiation of flowering. Proc. Natl Acad. Sci. USA 90, 287–291 (1993)
Swiezewski, S., Liu, F., Magusin, A. & Dean, C. Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target. Nature 462, 799–802 (2009)
Pierik, R. L. M. in Cellular and Molecular Aspects of Floral Induction (ed. Bernier, G.) 409–415 (Longmans, 1970)
Lee, I., Michaels, S. D., Masshardt, A. S. & Amasino, R. M. The late-flowering phenotype of FRIGIDA and mutations in LUMINIDEPENDENS is suppressed in the Landsberg erecta strain of Arabidopsis . Plant J. 6, 903–909 (1994)
Zhang, X. et al. Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis . PLoS Biol. 5, e129 (2007)
We thank all members of the C.D. and M.H. groups for discussions. We also thank S. Costa for suggestions to improve the FLC:GUS imagery and V. Grieneisen, S. Maree, R. Morris, S. Swiezewski and P. Wigge for comments on the manuscript. This research was supported by an Advanced Investigator European Research Council grant and the Core Strategic Grant from the Biotechnology and Biological Sciences Research Council to the John Innes Centre. M.H. also acknowledges support from The Royal Society.
The authors declare no competing financial interests.
About this article
Cite this article
Angel, A., Song, J., Dean, C. et al. A Polycomb-based switch underlying quantitative epigenetic memory. Nature 476, 105–108 (2011). https://doi.org/10.1038/nature10241
Frontiers in Plant Science (2021)
WIREs RNA (2021)
International Journal of Molecular Sciences (2021)
MLK4 ‐mediated phosphorylation of histone H3T3 promotes flowering by transcriptional silencing of FLC/MAF in Arabidopsis thalian a
The Plant Journal (2021)
Loss of EZH2-like or SU(VAR)3–9-like proteins causes simultaneous perturbations in H3K27 and H3K9 tri-methylation and associated developmental defects in the fungus Podospora anserina
Epigenetics & Chromatin (2021)