In this study we investigated the transcriptome and epigenome dynamics of the tomato fruit during post-harvest in a landrace belonging to a group of tomatoes(Solanum lycopersicum L.)collectively known as"Piennolo del Vesuvio",all characterized by a long shelf-life.Expression of protein-coding genes and microRNAs as well as DNA methylation patterns and histone modifications were analysed in distinct post-harvest phases.Multi-omics data integration contributed to the elucidation of the molecular mechanisms underlying processes leading to long shelf-life.We unveiled global changes in transcriptome and epigenome.DNA methylation increased and the repressive histone mark H3K27me3 was lost as the fruit progressed from red ripe to 150 days post-harvest.Thousands of genes were differentially expressed,about half of which were potentially epi-regulated as they were engaged in at least one epi-mark change in addition to being microRNA targets in~5%of cases.Down-regulation of the ripening regulator MADS-RIN and of genes involved in ethylene response and cell wall degradation was consistent with the delayed fruit softening.Large-scale epigenome reprogramming that occurred in the fruit during post-harvest likely contributed to delayed fruit senescence.