title: Knock-down of the methyltransferase Kmt6 relieves H3K27me3 and results in induction of cryptic and otherwise silent secondary metabolite gene clusters in Fusarium fujikuroi.
abstract: Filamentous fungi produce a vast array of secondary metabolites (SMs) and some play a role in agriculture or pharmacology. Sequencing of the rice pathogen Fusarium fujikuroi revealed the presence of far more SM-encoding genes than known products. SM production is energy-consuming and thus tightly regulated, leaving the majority of SM gene clusters silent under laboratory conditions. One important regulatory layer in SM biosynthesis involves histone modifications that render the underlying genes either silent or poised for transcription. Here, we show that the majority of the putative SM gene clusters in F. fujikuroi are located within facultative heterochromatin marked by trimethylated lysine 27 on histone 3 (H3K27me3). Kmt6, the methyltransferase responsible for establishing this histone mark, appears to be essential in this fungus, and knock-down of Kmt6 in the KMT6kdstrain shows a drastic phenotype affecting fungal growth and development. Transcription of four so far cryptic and otherwise silent putative SM gene clusters was induced in the KMT6kdstrain, in which decreased expression of KMT6 is accompanied by reduced H3K27me3 levels at the respective gene loci and accumulation of novel metabolites. One of the four putative SM gene clusters, named STC5, was analysed in more detail thereby revealing a novel sesquiterpene.
authors.affiliation: Institute of Plant Biology and Biotechnology, Westfälische Wilhelms-University Münster, 48143, Münster, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Studt
authors.affiliation: Institute of Plant Biology and Biotechnology, Westfälische Wilhelms-University Münster, 48143, Münster, Germany.|Institute of Food Chemistry, Westfälische Wilhelms-University Münster, 48149, Münster, Germany.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Rösler
authors.affiliation: Kekulé Institute for Organic Chemistry and Biochemistry, Rheinische Friedrich-Wilhelms-University Bonn, 53121, Bonn, Germany.
authors.forename: Immo
authors.initials: I
authors.lastname: Burkhardt
authors.affiliation: Institute of Food Chemistry, Westfälische Wilhelms-University Münster, 48149, Münster, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Arndt
authors.affiliation: Department of Biochemistry and Biophysics, Center for Genome Research and Biocomputing, Oregon State University, Corvallis, 97331, OR, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Freitag
authors.affiliation: Institute of Food Chemistry, Westfälische Wilhelms-University Münster, 48149, Münster, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.affiliation: Kekulé Institute for Organic Chemistry and Biochemistry, Rheinische Friedrich-Wilhelms-University Bonn, 53121, Bonn, Germany.
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Dickschat
authors.affiliation: Institute of Plant Biology and Biotechnology, Westfälische Wilhelms-University Münster, 48143, Münster, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Tudzynski
mesh_terms: D020816:Amino Acid Motifs; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005670:Fusarium / Q000737:chemistry / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D055785:Gene Knockdown Techniques; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D012275:Oryza / Q000382:microbiology*; D010935:Plant Diseases / Q000276:immunology / Q000382:microbiology*; D064210:Secondary Metabolism
chemical_list: D005656:Fungal Proteins; D006657:Histones; D008780:Methyltransferases