Appl Microbiol Biotechnol (2012) 95:1389–1404 to the cell cycle (Osmani et al. 1991a; Osmani et al. 1991b) and nitrogen regulation (Berger et al. 2006; Berger et al. 2008; Reyes-Dominguez et al. 2008) in A. nidulans. Histone modifications and the chromatin landscape in SM gene clusters The influence of histone modifying enzymes on SM pro- duction was first reported for ST production and gene reg- ulation by Shwab et al. (2007). In this initial work, the 1393 authors found that Aspergillus nidulans HDACs mutants, which were previously generated and characterized in the laboratory of Steve Graessle, bypass the requirement for the general SM activator LaeA (Bok and Keller 2004). Because histone acetylation generally acompanies gene activation it was reassuring to observe that lack of deacetylases or inac- tivation of their activity by deacetylase inhibitors leads to higher SM production in several fungi including Aspergil- lus, Penicillium, and Alternaria species. Employing chro- matin immunoprecipitation (ChIP, see Fig. 3 for a technical overview) in the sterigmatocystin cluster of A. nidulans, our Fig. 3 Technical outline of the Chromatin Immuoprecipitation (ChIP) procedure. (1) DNA and interacting proteins are cross- linked with formaldehyde. (2) Chromatin is shared into frag- ments of approximately equal size and precipitated with an antibody conjugated to mag- netic beads and specifically recognizing the modification in question (3). After several washing steps, the precipitated complex of antibody—protein —DNA is reverse cross-linked by incubation at high tempera- ture with NaCl (4). Purified DNA is quantified by qPCR using specific primers or ana- lysed by massive parallel se- quencing (MPS) (5)