title: Sound of silence: the beauvericin cluster in Fusarium fujikuroi is controlled by cluster-specific and global regulators mediated by H3K27 modification.
abstract: In this study, we compared the secondary metabolite profile of Fusarium fujikuroi and the histone deacetylase mutant ΔHDA1. We identified a novel peak in ΔHDA1, which was identified as beauvericin (BEA). Going in line with a 1000-fold increased BEA production, the respective non-ribosomal peptide synthetase (NRPS)-encoding gene (BEA1), as well as two adjacent genes (BEA2-BEA3), were significantly up-regulated in ΔHDA1 compared to the wild type. A special role was revealed for the ABC transporter Bea3: deletion of the encoding gene resulted in significant up-regulation of BEA1 and BEA2 and drastically elevated product yields. Furthermore, mutation of a conserved sequence motif in the promoter of BEA1 released BEA repression and resulted in elevated product levels. Candidate transcription factors (TFs) that could bind to this motif are the cluster-specific TF Bea4 as well as a homolog of the global mammalian Kruppel-like TF Yin Yang 1 (Yy1), both acting as repressors of BEA biosynthesis. In addition to Hda1, BEA biosynthesis is repressed by the activity of the H3K27 methyltransferase Kmt6. Consistently, Western blot analyses revealed a genome-wide enrichment of H3K27 acetylation (H3K27ac) in the ΔHDA1 and KMT6 knock-down mutants. Subsequent chromatin immunoprecipitation (ChIP) experiments showed elevated H3K27ac modification levels at the BEA cluster.
authors.affiliation: Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms-Universität Münster, Schlossplatz 8, Münster, D-48143.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Niehaus
authors.affiliation: Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms-Universität Münster, Schlossplatz 8, Münster, D-48143.
authors.forename: Lena
authors.initials: L
authors.lastname: Studt
authors.affiliation: Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, Münster, D-48149.
authors.forename: Katharina W
authors.initials: KW
authors.lastname: von Bargen
authors.affiliation: Institut für Genetik, Martin Luther Universität Halle-Wittenberg, Weinbergweg 10, Halle (Saale), D-06120.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Kummer
authors.affiliation: Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, Münster, D-48149.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.affiliation: Institut für Genetik, Martin Luther Universität Halle-Wittenberg, Weinbergweg 10, Halle (Saale), D-06120.
authors.forename: Gunter
authors.initials: G
authors.lastname: Reuter
authors.affiliation: Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms-Universität Münster, Schlossplatz 8, Münster, D-48143.
authors.forename: Bettina
authors.initials: B
authors.lastname: Tudzynski
mesh_terms: D000107:Acetylation; D047630:Depsipeptides / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005670:Fusarium / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D047630:Depsipeptides; D005656:Fungal Proteins; D014157:Transcription Factors; C004456:beauvericin; D008780:Methyltransferases; D006655:Histone Deacetylases