1390 as trichothecenes and aflatoxins produced by Fusarium and Aspergillus species, respectively, occur in contaminated grain, food, and feed products and act as carcinogens and mutagens (Gourama and Lloyd 1995; Trail 2009). Fungal toxins can also suppress the defense systems of plants infected by phytopathogenic fungi (Gardiner et al. 2010; Snijders 2004; Walter et al. 2010). Other secondary products, such as hydro- phobins, improve dispersal of spores and play an important role in the infection process of pathogens (Aimanianda et al. 2009; Kershaw and Talbot 1998). Siderophores are needed to solubilize iron for cellular uptake when intracellular iron pools are limiting (Haas 2003; Schrettl and Haas 2011). Secondary metabolites with medical benefit include antibiotics, immuno- suppressants, anti-hypercholesterol-, anti-osteoporotic-, and anti-tumor drugs (Brakhage 1998; Keller et al. 2005; Kennedy et al. 1999; Newman and Cragg 2007). The synthesis of all these metabolites is tightly controlled to avoid production and thus resource consumption under conditions where they are not needed. They are produced usually when macro- or micronutrients become limiting or when environmental factors such as humidity, temperature, UV irradiation, salt, or unfavorable pH values challenge the regular physiology of the cells (Hoffmeister and Keller 2007; Yu and Keller 2005). Due to the medical and eco- nomic importance of fungal SMs, genetic and physiological studies dealing with conditions and signals of SM produc- tion have been the subject of intense research. It is notewor- thy that, at least in Aspergillus species, SM production is linked with dark-induced sexual reproduction (Bayram et al. 2008; Calvo et al. 2002). In contrast, asexual reproduction and development of conidiospores is initiated when the fungal colony is exposed to an air interphase and light (Timberlake and Clutterbuck 1994). This way, a broad dis- persal of conidia in aerosols is possible. Co-production of dark-induced sexual fruiting bodies with secondary metab- olites, on the other hand, could have evolved because it ensured survival of the organism under competitive condi- tions where growth inside a substrate (dark and low oxygen concentration) would prevent aerosol dispersal of conidio- spores (David Canovas, personal communication). Howev- er, it is not yet well established whether other fungi link SM production with the darkness induced sexual cycle and the ecological significance of this regulatory mechanism remains to be verified. Some metabolic pathways such as the production of peni- cillin (PEN), sterigmatocystin (ST) and aflatoxin (AF) in Aspergillus species or deoxynivalenol (DON) and zearaleo- non (ZON) in Fusarium species served as model systems to understand the genetics of SM production (Brown et al. 1996; Diez et al. 1990; Hohn et al. 1995; MacCabe et al. 1990; Yu et al. 1995). The regulation of secondary metabolite production, and the connection to light, has been summarized and dis- cussed in a number of recent reviews (Bayram and Braus Appl Microbiol Biotechnol (2012) 95:1389–1404 2011; Calvo et al. 2002; Fox and Howlett 2008; Georgianna and Payne 2009; Schmidt-Heydt et al. 2009; Shwab and Keller 2008), and these basic aspects will not be discussed here unless they are directly related to chromatin-based regulation. Despite the enormous number of known metabolites, it is estimated that they represent only a small fraction of SMs fungi are able to produce in their natural habitats. These conclusions are drawn from genome sequencing projects which revealed a much higher number of potential second- ary metabolite genes compared to the actually known metabolites in each sequenced species (Chiang et al. 2011; Cuomo et al. 2007; Galagan et al. 2005). It is still unclear why most of the genes coding for polyketide synthases (PKSs) or nonribosomal peptide synthetases (NRPSs) are not expressed under the conditions in which we study them. The most probable reason is that usual laboratory growth conditions are significantly different from the conditions these organisms encounter in their natural habitats where they, to some extent, rely on SMs to protect their cells against harmful environmental conditions and for chemical warfare against competitors. However, at the moment, we cannot exclude the possibility that some of these predicted SM biosynthetic genes are not transcribed but persist in evolving fungal genomes without having a function in SM biosynthesis. For some of the well-studied metabolites such as aflatox- in, sterigmatocystin, or Deoxynivalenol researchers have learned to mimic natural production conditions in the labo- ratory and are able to generate the crucial signals which trigger the activation of these biosynthetic pathways. Why other SM genes are not activated by the same signals remains enigmatic. From an ecological perspective, differ- ent metabolites might be advantageous in different habitats where a given species will encounter different growth con- ditions and competitors. A prominent example in this re- spect is regulation of aflatoxin production in Aspergillus species by the nitrogen source: whereas Aspergillus nidu- lans produces highest ST levels (immediate precursor of AF) on nitrate as sole N-source, Aspergillus parasiticus promotes high AF levels on ammonium (Feng and Leonard 1998). Driven by the demand for new bio-pharmaceuticals a num- ber of genome mining expeditions have been launched during the past years. Different strategies based on bioinformatic analysis, overexpression of biosynthetic and regulatory genes or mimicry of natural habitats by co-cultivation of fungi and bacteria have been successfully applied during the last years to activate silent SM genes (Brakhage and Schroeckh 2011; Cichewicz 2009; Fisch et al. 2009). For example, genome- wide expression profiles recorded from strains lacking or over-expressing LaeA, the broad-domain SM regulator in A. nidulans (see below) led to the identification of terrequinone