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Eukaryotic Cell, September 2007, p. 1656-1664, Vol. 6, No. 9
1535-9778/07/$08.00+0     doi:10.1128/EC.00186-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Histone Deacetylase Activity Regulates Chemical Diversity in Aspergillus{triangledown}

E. Keats Shwab,1 Jin Woo Bok,1 Martin Tribus,2 Johannes Galehr,2 Stefan Graessle,2 and Nancy P. Keller1*

Plant Pathology Department, University of Wisconsin—Madison, 1630 Linden Drive, Madison, Wisconsin 53706,1 Division of Molecular Biology, Biocenter, Innsbruck Medical University, Fritz-Pregl Strasse 3, A-6020 Innsbruck, Austria2

Received 22 May 2007/ Accepted 27 June 2007

Bioactive small molecules are critical in Aspergillus species during their development and interaction with other organisms. Genes dedicated to their production are encoded in clusters that can be located throughout the genome. We show that deletion of hdaA, encoding an Aspergillus nidulans histone deacetylase (HDAC), causes transcriptional activation of two telomere-proximal gene clusters—and subsequent increased levels of the corresponding molecules (toxin and antibiotic)—but not of a telomere-distal cluster. Introduction of two additional HDAC mutant alleles in a {Delta}hdaA background had minimal effects on expression of the two HdaA-regulated clusters. Treatment of other fungal genera with HDAC inhibitors resulted in overproduction of several metabolites, suggesting a conserved mechanism of HDAC repression of some secondary-metabolite gene clusters. Chromatin regulation of small-molecule gene clusters may enable filamentous fungi to successfully exploit environmental resources by modifying chemical diversity.

* Corresponding author. Mailing address: Plant Pathology Department, Russell Laboratories, University of Wisconsin—Madison, 1630 Linden Drive, Madison, WI 53706. Phone: (608) 262-9795. Fax: (608) 263-2626. E-mail: npk{at}plantpath.wisc.edu

{triangledown} Published ahead of print on 6 July 2007.

Eukaryotic Cell, September 2007, p. 1656-1664, Vol. 6, No. 9
1535-9778/07/$08.00+0     doi:10.1128/EC.00186-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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