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Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans

Authors

  • Yazmid Reyes-Dominguez,

    1. Fungal Genetics and Genomics Unit, Austrian Institute of Technology (AIT) and University of Natural Resources and Applied Life Sciences (BOKU) Vienna, Austria.
    2. Institute de Génétique et Microbiologie, Université Paris-Sud, UMR 8621 CNRS, Orsay, France.
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    • §

      These authors contributed equally to this work.

  • Jin Woo Bok,

    1. Department of Plant Pathology, Department of Bacteriology and Department of Medical Microbiology and Immunology, UW-Madison, Madison, WI 53706, USA.
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    • §

      These authors contributed equally to this work.

  • Harald Berger,

    1. Fungal Genetics and Genomics Unit, Austrian Institute of Technology (AIT) and University of Natural Resources and Applied Life Sciences (BOKU) Vienna, Austria.
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    • Wellcome Trust Centre for Cell Biology, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK.

  • E. Keats Shwab,

    1. Department of Plant Pathology, Department of Bacteriology and Department of Medical Microbiology and Immunology, UW-Madison, Madison, WI 53706, USA.
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  • Asjad Basheer,

    1. Fungal Genetics and Genomics Unit, Austrian Institute of Technology (AIT) and University of Natural Resources and Applied Life Sciences (BOKU) Vienna, Austria.
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  • Andreas Gallmetzer,

    1. Fungal Genetics and Genomics Unit, Austrian Institute of Technology (AIT) and University of Natural Resources and Applied Life Sciences (BOKU) Vienna, Austria.
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  • Claudio Scazzocchio,

    1. Institute de Génétique et Microbiologie, Université Paris-Sud, UMR 8621 CNRS, Orsay, France.
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    • Present addresses: Department of Microbiology, Imperial College London, London, UK.

  • Nancy Keller,

    1. Department of Plant Pathology, Department of Bacteriology and Department of Medical Microbiology and Immunology, UW-Madison, Madison, WI 53706, USA.
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  • Joseph Strauss

    Corresponding author
    1. Fungal Genetics and Genomics Unit, Austrian Institute of Technology (AIT) and University of Natural Resources and Applied Life Sciences (BOKU) Vienna, Austria.
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E-mail joseph.strauss@boku.ac.at; Tel. (+43) 1 36006 6720; Fax (+43) 1 36006 6392.

Summary

Fungal secondary metabolites are important bioactive compounds but the conditions leading to expression of most of the putative secondary metabolism (SM) genes predicted by fungal genomics are unknown. Here we describe a novel mechanism involved in SM-gene regulation based on the finding that, in Aspergillus nidulans, mutants lacking components involved in heterochromatin formation show de-repression of genes involved in biosynthesis of sterigmatocystin (ST), penicillin and terrequinone A. During the active growth phase, the silent ST gene cluster is marked by histone H3 lysine 9 trimethylation and contains high levels of the heterochromatin protein-1 (HepA). Upon growth arrest and activation of SM, HepA and trimethylated H3K9 levels decrease concomitantly with increasing levels of acetylated histone H3. SM-specific chromatin modifications are restricted to genes located inside the ST cluster, and constitutive heterochromatic marks persist at loci immediately outside the cluster. LaeA, a global activator of SM clusters in fungi, counteracts the establishment of heterochromatic marks. Thus, one level of regulation of the A. nidulans ST cluster employs epigenetic control by H3K9 methylation and HepA binding to establish a repressive chromatin structure and LaeA is involved in reversal of this heterochromatic signature inside the cluster, but not in that of flanking genes.

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