SeMoVi Seminar, September 11
Location : Ecole Normale Superieure de Lyon (ENS Lyon), Blaise Pascal Conference Centre, LR6 building, room C 023, 46 allée d'Italie, Lyon. Map available here.
Free access. Contact: emilie.noguez(at)biosyl.org.
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2.00 - 3.00 |
Martin HOWARD John Innes Centre, UK |
Dissecting quantitative epigenetics through mathematical modelling and experiments |
|---|---|---|
| 3.00 - 3.30 | Coffee break | |
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3.30 - 4.00 |
Daniel JOST ENS Lyon, CNRS UMR 5672 |
Modeling epigenome folding: formation and dynamics of topologically-associated chromatin domains |
| 4.00 - 4.30 |
Jérôme GOVIN Team EDyP (Exploring the Dynamics of Proteomes) "Large Scale Biology" Unit, Grenoble |
Epigenetics and chromatin dynamics in gametes |
| 4.30 - 5.00 | General discussion |
Dissecting quantitative epigenetics through mathematical modelling and experiments
Martin Howard, John Innes Centre, UK
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 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 (digital) 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 digital, on or off pattern of FLC gene expression in individual cells, a prediction we verified using the FLC:GUS reporter system. I will also present new results, implicating H3K36me3 as the “opposing” mark to H3K27me3. We are also examining the nature of temperature registration during cold exposure itself, which intriguingly may also be a digital, all or nothing process inside individual cells.
Modeling epigenome folding: formation and dynamics of topologically-associated chromatin domains
Daniel Jost, Laboratoire de Physique, Ecole Normale Supérieure de Lyon, CNRS UMR 5672, Lyon, 69007
Genomes of eukaryotes are partitioned into domains of functionally distinct chromatin states. These domains are stably inherited across many cell generations and can be remodelled in response to developmental and external cues, hence contributing to the robustness and plasticity of expression patterns and cell phenotypes. Remarkably, recent studies indicate that these one-dimensional epigenomic domains tend to fold into three-dimensional topologically-associated domains forming specialized nuclear chromatin compartments. However, the general mechanisms behind such compartmentalization including the contribution of epigenetic regulation remain unclear. Here, we address the question of the coupling between chromatin folding and epigenome. Using polymer physics, we analyze the properties of a block copolymer model that accounts for local epigenomic information. Considering copolymers build from the epigenomic landscape of Drosophila, we observe a very good agreement with the folding patterns observed in chromosome conformation capture experiments. Moreover, this model provides a physical basis for the existence of multistability in epigenome folding at sub-chromosomal scale. We show how experiments are fully consistent with multistable conformations where topologically-associated domains of the same epigenomic state interact dynamically with each other. Our approach provides a general framework to improve our understanding of chromatin folding during cell-cycle and differentiation and its relation to epigenetics.
Epigenetics and chromatin dynamics in gametes
Jérôme Govin, Team EDyP (Exploring the Dynamics of Proteomes), Unité "Large Scale Biology", Grenoble
(More information: http://www.epigam.fr, Grenoble Chromatin club: http://epigenetics.fr)
Gametes are crucial cells, essential for the survival of mammals, as well as other animals, plants, fungi and even lower eukaryotes. Their nucleus is highly compact and has been pre-programmed for embryonic development. Nevertheless, how their chromatin is organized remains poorly understood. The study of gametes in higher eukaryotes is limited by the technical methods available, which are often expensive and time-consuming. We revealed that a simple yeast spore model shares functional epigenetic similarities with mammalian sperm. This makes yeast spores a unique and powerful model to study gametes and the organization of their chromatin. We are implementing ambitious exploratory approaches combining genetics, biochemistry, structural biology and proteomics to conduct a systematic investigation of chromatin reorganization during sporulation. Here, the functional role of Bdf1, a protein containing 2 bromodomains and essential in gamete chromatin biology will be presented. Integrative approaches are currently developed, with detailed in vitro and in vivo functional analysis. New results will be extended to BET proteins in mammalian models, particularly during gametogenesis.
Download poster here
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