Shwab E Keats, Bok Jin Woo, Tribus Martin, Galehr Johannes, Graessle Stefan, Keller Nancy P
Plant Pathology Department, Russell Laboratories, University of Wisconsin--Madison, 1630 Linden Drive, Madison, WI 53706, USA.
Eukaryot Cell. 2007 Sep;6(9):1656-64. doi: 10.1128/EC.00186-07. Epub 2007 Jul 6.
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.
生物活性小分子在曲霉属物种的发育及其与其他生物体的相互作用过程中至关重要。负责其产生的基因编码在可位于整个基因组中的簇中。我们发现，编码构巢曲霉组蛋白脱乙酰酶（HDAC）的hdaA缺失会导致两个端粒近端基因簇的转录激活——以及相应分子（毒素和抗生素）水平的随后增加——但不会导致端粒远端簇的转录激活。在ΔhdaA背景中引入另外两个HDAC突变等位基因对两个受HdaA调控的簇的表达影响最小。用HDAC抑制剂处理其他真菌属会导致几种代谢物的过量产生，这表明HDAC对一些次生代谢物基因簇的抑制机制具有保守性。小分子基因簇的染色质调控可能使丝状真菌能够通过改变化学多样性来成功利用环境资源。
