SYSTEMS BIOLOGY SEMINAR SERIES 2012 "Dissecting quantitative epigenetic silencing through mathematical modelling and experiments"

Date:
30 Jan 2012, 14:00 - 15:00

Abstract :


Vernalization, the perception and memory of winter in plants, is a classic epigenetic process that involves epigenetic silencing of the floral repressor gene FLC. 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. The silencing is believed to be mediated by the addition of covalent modifications to histones, in this case trimethylation of histone 3 lysine 27 (H3K27me3). Using mathematical modelling, chromatin immunoprecipitation and an FLC:GUS reporter assay, we have shown [1] 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 verified using the FLC:GUS reporter system.


[1] Angel, Song, Dean, Howard:A Polycomb-based switch underlying quantitative epigenetic memory Nature 476 105-108 (2011)


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The Systems Biology Seminar series is designed to showcase the power of quantitative and computational methods in providing new insights to experimental biology and connecting diverse biological scales; as well as highlighting the integration of biological, physical, mathematical and computational approaches in the life sciences.


 To get the series off to a flying start, the organising committee has selected a stellar cast of speakers for 2012, including Martin Howard (John Innes Centre, Norwich), Benjamin Simons (University of Cambridge), Hans Meinhardt (Max Plank Institute, Tubingen), Bella Novak (University of Oxford) and Frank Julicher (Max Plank Institute, Dresden).


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Type of Event:
Seminar

Speaker:
Professor Martin Howard

Location:
MSI Small Lecture Theatre

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