Assessing the impact of DNA methylation loss on genome stability: a quantitative genetics perspective – EPIMOBILE

Using a unique population of so-called 'epigenetic' Recombinant Inbred Lines (epiRILs) in the flowering plant Arabidopsis thaliana, we have recently demonstrated that multiple DNA methylation changes induced across the genome can be stably inherited for at least eight generations in the absence of selection, and that these changes could provide a substantial source of heritable variation in two complex traits. We now wish to explore the molecular nature of the changes that underlie this heritable variation. Given the know function of DNA methylation in preserving genome integrity, notably through the silencing of transposable elements, we propose to sequence the genome a large number of epiRILs using next-generation sequencing technologies to determine the full spectrum of DNA sequence changes induced as a result of severe DNA methylation alterations across the genome. This analysis will be coupled to that of methylation polymorphisms in the same lines in order to provide robust information on the tempo and type of DNA sequence changes associated in cis with DNA methylation alterations. In addition, genome sequencing will provide precise estimates of the number and the identity of transposable elements that are mobilized as a result of altered DNA methylation. Bioinformatic analysis of mobile and non-mobile elements as well as genetic and molecular tests will be carried out to identify the determinants of transposable element mobilization. This project will also provide a list of QTL generated through genome-wide alteration of DNA methylation, for which the cause of variation is identified (DNA sequence or heritable DNA methylation change, or both) and which affect flowering time.