Considering the forecasted world demographic growth and the global changes in climate, it is becoming a major challenge for human society to provide sufficient amounts of high nutritional and sensory quality food. The TomEpiSet project aims to uncover new means and strategies to overcome poor fruit setting and the resulting low yield under elevated temperature using tomato as reference species. Screen tomato germoplasm and available auxin related and epigenetic mutants to select lines that successfully initiate fruit setting without need for pollination, normal or high yield with maintenance of fruit quality under heat stress conditions. The main novelty of the project is to unravel of the epigenetic components of the fruit set process and parthenocarpy in relation to auxin signaling. Genome-wide transcriptomic profiling combined to chromatin immuno-precipitation and DNA methylation studies will generate extensive multidimensional expression maps of epigenetic marks and auxin signaling factors allowing uncovering new components of the fruit set process. These new candidate genes will be analyzed with reverse genetics approaches using transgenic lines mis-expressing these genes to generate loss-of-function mutants by CRISPR/cas9 - RNAi approaches or overexpression plants. Then, the mutant plants will be analyzed at the physiological level for their capacity to produce normal or higher fruit yields in conditions of elevated ambient temperatures. An attempt to setup a new approach for breading using epigenetic information will be developed in the frame of the project. Programmable epigenetic marks based on the CRISPR/Cas9 gene regulation system, consisting of the nuclease-null dCas9 protein fused to the catalytic core histone or DNA modifiers will be in generated to guide for specific epigenetic modifications to candidate genes identified by an integrated approach combining RNA-Seq, ChIP-Seq and BS-Seq approaches. Validated epi-mutants will be phenotyped regarding their ability to display normal or higher fruit yield under elevated temperatures without loss of fruit quality. A major goal of our project will be the integration of all data sets coming from different high throughput approaches. TomEpiSet will take advantage of the tomato transcriptomic platform called TomExpress (http://gbf.toulouse.inra.fr/tomexpress) which has been developed by P1, allows processing and analyzing the data in standardized and unified ways for the whole project. Elucidating the mechanisms underpinning fruit set by integrating epigenetic mechanisms and auxin signaling will represent a major breakthrough in our understanding of reproductive biology and will open the way to the design of new strategies towards improving crop yield, particularly in adverse environmental condition leading to poor flower fertilization. TomEpiSet will highly contribute to enrich the content of high education courses at the national and international level through an Erasmus+ Capacity Building in the Field of Higher Education ‘MABIOVA’ (creation of a Master degree in plant Biotechnology field) project coordinated by P1 and through different partners of the project regarding their involvement in teaching activities at the high education level. The use of our data for tomato breeding will be in the scope of the valorization procedures and we shall use the Partners’ national and international network of contacts, for such perspectives.