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FP7

MEDEA Report Summary

Project reference: 250358
Funded under: FP7-IDEAS-ERC

Final Report Summary - MEDEA (Mechanisms of Epigenetic regulation in Development, Evolution and Adaptation)

Over the last decade epigenetic gene regulation has become a major focus of scientific research as it was shown to play an important role in plant and animal development but also as a cause of human disease. Until recently, however, a role of epigenetic processes in evolution has found little general support. The goal of this ERC project was to understand the complex interplay of epigenetic mechanisms in plant development and evolution. To achieve this goal, we focused on two epigenetic paradigms. On the one hand, we focused on dissecting the mechanisms of genomic imprinting at the MEDEA (MEA) locus in Arabidopsis, which was investigated using genetic, molecular, and biochemical approaches to gain a comprehensive picture of the complex interplay of various epigenetic pathways. On the other hand, we analyzed the role of epigenetic variation in adaptation and evolution using an experimental selection approach in Arabidopsis, and by studying a stable, heritable, epigenetic switch occurring in certain populations of Mimulus aurantiacus. In this non-model system, an epigenetic switch of the pollinator syndrome leads to reproductive isolation and, therefore, affects population structure and, thus, the evolutionary trajectory of the species. The various experimental systems each offer unique opportunities to shed light onto the underlying mechanisms controlling epigenetic states in both developmental and evolutionary processes. Such a holistic approach to understand the role of epigenetic regulation from the molecular to the ecosystem level has rarely been undertaken and our studies have provided new insights into both the mechanism of epigenetic regulation during development and the role of heritable, epigenetic variation in ecology and evolution.
To elucidate the molecular pathways and their complex interplay in the regulation of genomic imprinting at the MEA locus, we identified several novel factors regulating imprinting using a genetic screen for loss of imprinting of transgenic reporter gene where the MEA Imprinting Control Region (ICR), which is not methylated (Wöhrmann et al., 2012), drives imprinted expression of a GUS reporter gene. The cloning of these EMS-induced mutants using our newly established methodology (Lindner et al., 2012) turned out to be challenging, however, likely due to genome instabilities caused by these mutations. The identification of two imprinting regulators is currently ongoing using alternative strategies. Furthermore, quantitative genetic methods identified several paternal modifiers of imprinting (Pires et al., 2016). We could also show that DNA methylation and histone H3K27me3 methylation cooperate rather than exclude each other, at least as some imprinted loci (Schmidt et al., 2013). To molecularly test a model for MEA imprinting that involves higher order chromatin structure, i.e. chromatin looping (Wöhrmann et al., 2012), we successfully established Chromosome Conformation Capture (3C)-based technologies in plants. However, the highly streamlined, gene-dense Arabidopsis genome turned out to be unsuitable for the identification of enhancer-promoter interactions or chromatin loops by 4C or Hi-C, while this methodology allows a detailed characterization of the three dimensional organization of the genome (Grob et al., 2013) and led to the identification of a novel, evolutionary conserved nuclear structure, the KNOT (Grob et al., 2014). Finally, the biochemically characterization of MEA-containing complexes and their targets is still ongoing and, so far, has led to the development of novel, biochemical tools allowing the in vivo labeling and observation of proteins.
To investigate the role of epigenetic regulation in plant evolution and adaptation, we analyzed the epigenetic response to selection in experimental populations of Arabidopsis. While we could not demonstrate an epigenetic memory of stress in epigenetically highly uniform populations (Grob et al., in preparation), we could clearly show that standing, epigenetic variation is subject to selection and find phenotypic changes that are heritable for at least 2-3 generation in the absence of selection in three independent, replicated selection experiments (Schmid et al., in preparation). We developed new bioinformatics tools based on linear models to compare multiple methylomes with each other. To our knowledge, this is the first example showing selection of phenotypic traits in the absence of genetic variation that is fully supported by whole-genome molecular analyses. Finally, we have now firmly established the epigenetic nature of the switch in pollinator syndrome in Mimulus (Hirsch et al. 2012), using genetic crossing experiments and field studies (Baumberger & Grossniklaus, in prepration). To further elucidate the relationship between phenotypic change and epigenetic regulation we established a refernce transcrptome (Hirsch et al., in preparation) and identified several transcription factors correlated with phenotypic changes, which we are currently characterizing further at the molecular and functional level (Steinbach et al., in preparation).

Contact

Grossniklaus, Ueli (Principal Investigator)
Tel.: +41 44 632 53 50
Fax: +41 44 632 53 51
E-mail
Record Number: 187729 / Last updated on: 2016-08-16