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A Polycomb-based switch underlying quantitative epigenetic memory


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.

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Figure 1: H3K27me3 ChIP experiments.
Figure 2: Schematic outline of mathematical model for FLC silencing.
Figure 3: Fitting model output to experimental ChIP data.
Figure 4: Validating model predictions.


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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.

Author information




C.D. and M.H. conceived the study, A.A., J.S., C.D. and M.H. designed the experiments, J.S. performed the experiments, A.A. and J.S. analysed the experimental data, A.A. and M.H. designed the numerical simulations, A.A. performed the simulations and analysed the simulation data. A.A., J.S., C.D. and M.H. wrote the manuscript.

Corresponding authors

Correspondence to Caroline Dean or Martin Howard.

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The authors declare no competing financial interests.

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The file contains Supplementary Text, Supplementary Figures 1-12 with legends, Supplementary Tables 1-2 and additional references. (PDF 929 kb)

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Angel, A., Song, J., Dean, C. et al. A Polycomb-based switch underlying quantitative epigenetic memory. Nature 476, 105–108 (2011).

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