The specific interaction between A. nidulans and S. rapamycinicus now provides an excellent model system to elucidate the underlying molecular mechanisms leading to the activation of a silent secondary metabolism gene cluster by a bacterium. Based on these previous findings, in this proposal, we will (i) identify the entirely unknown signals deriving from the bacterium by applying a transposon knock-out library and, moreover, the corresponding fungal receptors like components of the Saga/Ada complex leading to the activation of the ors gene cluster, (ii) identify the downstream targets of the chromatin-modifying Saga/Ada complex in response to the bacterium by RNA sequencing and proteome analyses of the histone acetyltransferase gcnE mutant, (iii) identify counteracting HDACs and their complexes and (iv) elucidate how chromatin-modifying complexes are targeted to certain regions of the chromosome in response to specific bacterial signals. This will be achieved by analyzing the protein complexes on the ors promoters under standard (non-inducing) and inducing conditions during co-cultivation of bacterium and fungus by chromatin immune precipitation of proteins cross-linked to the DNA of the promoters of ors genes. (v) Finally, we will identify the impact of orsellinic acid and its derivatives on structuring microbial communities or, at least, on other microorganisms. These studies will provide fundamental insights into epigenetic regulation of secondary metabolites in response to microbial communication and will potentially allow insights into entirely novel mechanisms of epigenetic control of gene clusters.