Histone deacetylase activity regulates chemical diversity in Aspergillus.
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 DeltahdaA 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.
Shwab
E Keats
EK
Plant Pathology Department, Russell Laboratories, University of Wisconsin--Madison, 1630 Linden Drive, Madison, WI 53706, USA.
Bok
Jin Woo
JW
Tribus
Martin
M
Galehr
Johannes
J
Graessle
Stefan
S
Keller
Nancy P
NP
D000483:Alleles; D001233:Aspergillus nidulans / Q000737:chemistry* / Q000201:enzymology* / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family / Q000235:genetics* / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics
D002843:Chromatin; D005656:Fungal Proteins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases