title: Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation.
abstract: Sequence analyses of fungal genomes have revealed that the potential of fungi to produce secondary metabolites is greatly underestimated. In fact, most gene clusters coding for the biosynthesis of antibiotics, toxins, or pigments are silent under standard laboratory conditions. Hence, it is one of the major challenges in microbiology to uncover the mechanisms required for pathway activation. Recently, we discovered that intimate physical interaction of the important model fungus Aspergillus nidulans with the soil-dwelling bacterium Streptomyces rapamycinicus specifically activated silent fungal secondary metabolism genes, resulting in the production of the archetypal polyketide orsellinic acid and its derivatives. Here, we report that the streptomycete triggers modification of fungal histones. Deletion analysis of 36 of 40 acetyltransferases, including histone acetyltransferases (HATs) of A. nidulans, demonstrated that the Saga/Ada complex containing the HAT GcnE and the AdaB protein is required for induction of the orsellinic acid gene cluster by the bacterium. We also showed that Saga/Ada plays a major role for specific induction of other biosynthesis gene clusters, such as sterigmatocystin, terrequinone, and penicillin. Chromatin immunoprecipitation showed that the Saga/Ada-dependent increase of histone 3 acetylation at lysine 9 and 14 occurs during interaction of fungus and bacterium. Furthermore, the production of secondary metabolites in A. nidulans is accompanied by a global increase in H3K14 acetylation. Increased H3K9 acetylation, however, was only found within gene clusters. This report provides previously undescribed evidence of Saga/Ada dependent histone acetylation triggered by prokaryotes.
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, 07745 Jena, Germany.
authors.forename: Hans-Wilhelm
authors.initials: HW
authors.lastname: Nützmann
authors.forename: Yazmid
authors.initials: Y
authors.lastname: Reyes-Dominguez
authors.forename: Kirstin
authors.initials: K
authors.lastname: Scherlach
authors.forename: Volker
authors.initials: V
authors.lastname: Schroeckh
authors.forename: Fabian
authors.initials: F
authors.lastname: Horn
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gacek
authors.forename: Julia
authors.initials: J
authors.lastname: Schümann
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.forename: Joseph
authors.initials: J
authors.lastname: Strauss
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
mesh_terms: D000107:Acetylation; D001233:Aspergillus nidulans / Q000201:enzymology* / Q000235:genetics; D055162:Biocatalysis; D001688:Biological Products / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008954:Models, Biological; D005810:Multigene Family / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012118:Resorcinols / Q000378:metabolism; D012459:Salicylates / Q000378:metabolism; D013241:Sterigmatocystin / Q000378:metabolism; D013302:Streptomyces / Q000502:physiology*
chemical_list: D001688:Biological Products; D005656:Fungal Proteins; D006657:Histones; D012118:Resorcinols; D012459:Salicylates; D013241:Sterigmatocystin; C501612:orsellinic acid; C008263:lecanoric acid; D051548:Histone Acetyltransferases