Appl Microbiol Biotechnol (2012) 95:1389–1404 additional trigger could be some sort of stress imposed on A. nidulans cultures by bacterial cells. In support of such a mechanism Linz and colleagues recently found that the oxidative stress pathway mediated by cAMP-response ele- ments is involved in the activation of the aflatoxin gene cluster in A. parasiticus (Roze et al. 2011). Thus, one of several plausible signaling pathways to unlock orsellinic acid production by bacterial contact could also involve an oxidative stress-related pathway that co-activates Saga/Ada. Although involvement of Saga/Ada or H3 acetylation has not been reported for SM regulation in A. parasiticus, it is known that histone H4 hyper-acetylation parallels the acti- vation of genes within the aflatoxin cluster (Roze et al. 2007). H4 acetylation also seems to play a role in A. nidu- lans SM regulation. Four gene clusters were recently exam- ined for this chromatin mark (sterigmatocystin, penicillin, terrequinone, and orsellinic acid) by Soukup et al. (2012). In this work, the authors found augmented H4K12 acetylation 1397 in the tested SM clusters during the secondary metabolite production phase. Based on suppressor screens and over- expression studies, the essential EsaA histone acetyltrans- ferase was suggested to be responsible for this chromatin acetylation pattern. EsaA is the A. nidulans orthologue of Esa1, the catalytic subunit of the essential S. cerevisiae NuA4 transcriptional adaptor/acetyltransferase complex in- volved in H2A and H4 acetylation, cell cycle control, and epigenetic control of transcription (Allard et al. 1999; Doyon and Cote 2004; Galarneau et al. 2000). Clearly, H4 acetylation by EsaA requires functional LaeA, suggesting that this general activator of SM and member of the velvet complex (Bayram and Braus 2011; Bayram et al. 2008; Sarikaya Bayram et al. 2010) participate in recruitment of the putative A. nidulans NuA4 complex. This is in contrast to H3 acetylation where this general regulator does not seem to play an essential role in recruitment of the Saga/Ada complex. (Figure 5 shows a side-by-side comparison of Fig. 5 Different SM biosynthetic clusters respond to different activa- tion pathways. Some of the clusters possess pathway specific activa- tors, e.g., AflR regulating the ST cluster, while in some clusters the involvement of broad domain regulators have been shown, e.g., the pH regulator PacC is required to turn on the PEN cluster. Functional and probably physical interaction between HepA and ClrD negatively regulates the expression of all tested SM gene clusters. The function of CclA, part of the putative Set1 methyltransferase complex, was found to only inhibit the expression of genes within the MDP and ORS clusters, partially via a positive action on HepA/ClrD. The complexity of this regulatory network is illustrated by the interplay between LaeA, which negatively influence HepA/ClrD function but stimulates the function of EsaA in acetylating H4K12. Interestingly, the aatB gene involved in penicillin biosynthesis but located on chro- mosome I outside of PEN cluster, is not co-regulated by chromatin remodelling proteins. Arrows and plus symbols indicate activation, block lines, and minus symbols represent inhibition