Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production

Authors

  • Alexandra A. Soukup,

    1. Department of Genetics, University of Wisconsin-Madison, Madison, WI, USA
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  • Yi-Ming Chiang,

    1. Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
    2. Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA
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  • Jin Woo Bok,

    1. Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA
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  • Yazmid Reyes-Dominguez,

    1. Fungal Genetics and Genomics Unit, University of Natural Resources and Life Sciences Vienna, Austria
    2. Austrian Institute of Technology GmbH, University and Research Center Campus Tulln, Tulln/Donau, Austria
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  • Berl R. Oakley,

    1. Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA
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  • Clay C. C. Wang,

    1. Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA
    2. Department of Chemistry, University of Southern California, Los Angeles, CA, USA
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  • Joseph Strauss,

    1. Fungal Genetics and Genomics Unit, University of Natural Resources and Life Sciences Vienna, Austria
    2. Austrian Institute of Technology GmbH, University and Research Center Campus Tulln, Tulln/Donau, Austria
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  • Nancy P. Keller

    Corresponding author
    1. Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA
    • Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA
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For correspondence. E-mail npkeller@wisc.edu; Tel. (608) 262 9795; Fax (608) 262 8418.

Summary

Regulation of secondary metabolite (SM) gene clusters in Aspergillus nidulans has been shown to occur through cluster-specific transcription factors or through global regulators of chromatin structure such as histone methyltransferases, histone deacetylases, or the putative methyltransferase LaeA. A multicopy suppressor screen for genes capable of returning SM production to the SM deficient ΔlaeA mutant resulted in identification of the essential histone acetyltransferase EsaA, able to complement an esa1 deletion in Saccharomyces cereviseae. Here we report that EsaA plays a novel role in SM cluster activation through histone 4 lysine 12 (H4K12) acetylation in four examined SM gene clusters (sterigmatocystin, penicillin, terrequinone and orsellinic acid), in contrast to no increase in H4K12 acetylation of the housekeeping tubA promoter. This augmented SM cluster acetylation requires LaeA for full effect and correlates with both increased transcript levels and metabolite production relative to wild type. H4K12 levels may thus represent a unique indicator of relative production potential, notably of SMs.

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