You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Sound of silence: the beauvericin cluster in Fusarium fujikuroi is controlled by cluster‐specific and global regulators mediated by H3K27 modification
Published in:
Environmental Microbiology, 18 (2016) 11, Seite 4282-4302
Language:
English
DOI:
10.1111/1462-2920.13576
ISSN:
1462-2912;
1462-2920
Origination:
Footnote:
Description:
SummaryIn 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.