1396 AreA function in nitrogen regulation is conserved in all fungi and media shift experiments were performed to cir- cumvent this problem in the plant pathogen Gibberella fujikuroi. In this organism, Giberellin (GA) production and the expression of the corresponding biosynthetic genes is under the control of FfAreA (Wagner et al. 2010). Whether AreA is acting only as transcriptional co-activator or also required for histone acetylation and subsequent chromatin remodeling at the GA cluster awaits clarification. Increasing the level of histone acetylation at SM clusters was also found to be the molecular basis of how bacterial- fungal co-cultivation activates silent clusters in A. nidulans. In an earlier study, Schroeckh and coworkers (2009) reported that direct physical interaction of A. nidulans and a specific strain of the soil-dwelling bacterium Streptomyces rapamycinicus resulted in the activation of a large silent cluster containing biosynthetic genes for orsellinic acid, lecanoric acid, and the cathepsin K inhibitors F-9775A and F-9775B. In a recent follow-up study, Nützmann and col- leagues (2011) could demonstrate that bacterial co- cultivation generates the signal for Saga/Ada-mediated H3K9 and K14 acetylation, providing a molecular explana- tion for the ORS cluster activation under these conditions. Because inhibition of histone deacetylases by SAHA pheno- copies bacterial co-cultivation bacteria could generate a signal that hyper-activates Saga/Ada or inhibits H3 deace- Appl Microbiol Biotechnol (2012) 95:1389–1404 tylation, or both. The fact that we found by ChIP more GcnE-FLAG at ORS cluster promoters during co- cultivation, however, indicates that increased Saga/Ada ac- tivity is at least one mechanism contributing to the observed effect. It is interesting to note that H3 acetylation marks are different inside and immediately outside the ORS cluster (Fig. 4a). Whereas H3K14 acetylation can be found inside the cluster but also in the neighboring region, H3K9 hyper- acetylation following bacterial stimulation can only be detected within the cluster. The crucial role for H3K9 in defining the borders of a cluster was already shown for ST (Reyes-Dominguez et al. 2010) and for MDP (Bok et al. 2009) (see Fig. 4b). Therefore, this mark surely plays a key role in defining the transcriptional activity of genes belong- ing to a defined cluster and might even be used to predict the limits of unknown biosynthetic clusters. If the respective H3K9 modification is involved in setting the exact borders or if the pre-defined borders define H3K9 marks between these limits is currently unknown. How the signal for Saga/Ada activation or HDAC inac- tivation is generated also remains a matter of speculation, especially as an intimate contact between the organisms is required to trigger this effect. One possibility might be nutrient competition, but the fact that only one specific isolate of many strains tested was able to trigger the activa- tion event makes this mechanism unlikely. Another or an Fig. 4 Activation of SM gene clusters. In some cases the recruitment of positive regulators is required to activate silent SM gene clusters, whereas in other cases removal of negative regulators is sufficient. a Co-incubation of A. nidulans with S. rapamycinicus leads to increased acetylation of histone H3 lysine 9 (cluster specific) and lysine 14 (cluster unspecific) what results in sub- sequent activation of the ORS cluster. b Deletion of CclA leads to reduced H3K4me3 levels at a large genomic region including the MDP gene cluster however only at genes belong to the cluster H3K9me3 is de- creased, what is sufficient to activate the otherwise silent MDP pathway