We identified four epigenetic quantitative trait loci (epiQTL) providing heritable resistance without negative consequences for plant growth or resistance to different (a)biotic stresses. Our study provides proof-of-concept that modification of plant DNA methylation can yield heritable disease resistance without major non-target effects.. Epigenetic basis of transgenerational immune priming in Arabidopsis

DNA methylation in plants transmits trans-generational epigenetic information, which affects diverse traits independently of genetic variation. Recent evidence suggests that DNA methylation regulates priming of plant immunity, which increases the responsiveness of plant immune system resulting in enhanced resistance to pathogens. In this study, we screened an Arabidopsis population of epigenetic recombinant inbred lines (epiRILs) for disease resistance against Hyaloperonospora arabidopsidis (Hpa). We identified four epigenetic quantitative trait loci (epiQTL) providing heritable resistance without negative consequences for plant growth or resistance to different (a)biotic stresses. RNA-sequencing analysis of Hpa-resistant epiRILs revealed the resistance is based on genome-wide priming of defence-related genes, providing first causal evidence for the role of DNA methylation in defence priming. Through analysis of DNA methylation and chromatin interactions at the epiQTLs, we propose a novel trans-regulatory mechanism by which methylation-sensitive chromatin interactions contribute to transgenerational immune priming. Our study provides proof-of-concept that modification of plant DNA methylation can yield heritable disease resistance without major non-target effects.