Plants have evolved efficient molecular mechanisms to cope with adverse environmental conditions, and an adaptative strategy to remember past environmental stress, namely stress memory, to respond quickly to stress when it occurs again. The plant hormone abscisic acid (ABA) plays a key role in response to environmental cues, and it can work as priming agent mimicking a stress to equip plants with faster and more efficient responses against future stresses. An epigenetic control in plant responses to abiotic stress, as well as in the stress memory adaptative phenomenon, has been clearly proven in the last decade. Despite extensive evidence on epigenetically regulated stress-induced genes, a genome-wide scenario of epigenetic modifications in response to environmental stresses is still missing. The field of drug discovery has been widely used in animal systems, while in plants it is only recently becoming popular. Although chemical inhibition of epigenetic markers provides an effective approach to study and influence epigenetic modifications, so far it has not been widely exploited. The consortium presenting this project has previously assessed the efficacy and selectivity of the compound RDS 3434, an inhibitor of the human catalytic subunit of Polycomb Repressive Complex2 (PRC2), on Arabidopsis seeds and seedlings. Since RDS 3434 is effective in inhibiting PRC2 activity and PRC2 is involved in plant response to abiotic stress, this project aims to carry out a case study, assessing the effects of the RDS 3434 epidrug in response to a stress-mimicking ABA treatment in Arabidopsis thaliana, both at physiological and transcriptomic level. To further exploit the potential of the use of epigenetic drug compounds, this project aims to identify new epidrugs able to affect the epigenetic molecular mechanisms underlying the control of ABA-mediated responses to abiotic stresses (i.e. cold, salt). To this end, an experimental setup designed to monitor these responses will be used to screen a library of chemical compounds developed against various epigenetic markers, previously synthesized and tested for efficacy and specificity in human cells by a member of the consortium. The hit compounds identified will be optimized, through a rational drug design approach. The effects of the new epidrug on the epigenomic landscape of Arabidopsis plants under a stress-mimicking ABA treatment will be assessed. The efficacy of RDS 3434 and the new epidrug to affect Arabidopsis response to cold and salt stress will be evaluated at both physiological and transcriptomic level. In addition, aim of this project is to transfer knowledge acquired in Arabidopsis to two species of remarkable agronomic interest, tomato and grapevine, so as to give this project, in addition to the strong scientific content, a remarkable agronomic value.