Fungal Genetics and Genomics Unit, Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Science Vienna, Austria.
Fungal Genet Biol. 2012 Jan;49(1):39-47. doi: 10.1016/j.fgb.2011.11.002. Epub 2011 Nov 11.
Chromatin modifications and heterochromatic marks have been shown to be involved in the regulation of secondary metabolism gene clusters in the fungal model system Aspergillus nidulans. We examine here the role of HEP1, the heterochromatin protein homolog of Fusarium graminearum, for the production of secondary metabolites. Deletion of Hep1 in a PH-1 background strongly influences expression of genes required for the production of aurofusarin and the main tricothecene metabolite DON. In the Hep1 deletion strains AUR genes are highly up-regulated and aurofusarin production is greatly enhanced suggesting a repressive role for heterochromatin on gene expression of this cluster. Unexpectedly, gene expression and metabolites are lower for the trichothecene cluster suggesting a positive function of Hep1 for DON biosynthesis. However, analysis of histone modifications in chromatin of AUR and DON gene promoters reveals that in both gene clusters the H3K9me3 heterochromatic mark is strongly reduced in the Hep1 deletion strain. This, and the finding that a DON-cluster flanking gene is up-regulated, suggests that the DON biosynthetic cluster is repressed by HEP1 directly and indirectly. Results from this study point to a conserved mode of secondary metabolite (SM) biosynthesis regulation in fungi by chromatin modifications and the formation of facultative heterochromatin.
染色质修饰和异染色质标记已被证明参与了真菌模型系统 Aspergillus nidulans 中次生代谢基因簇的调控。我们在这里研究了 Fusarium graminearum 的异染色质蛋白同源物 HEP1 对次生代谢产物产生的作用。在 PH-1 背景下删除 Hep1 会强烈影响产生 aurofusarin 和主要的三萜烯代谢物 DON 的基因的表达。在 Hep1 缺失菌株中,AUR 基因高度上调,aurofusarin 的产量大大提高,这表明异染色质对该基因簇的基因表达具有抑制作用。出乎意料的是,三萜烯基因簇的基因表达和代谢物水平较低,这表明 Hep1 对 DON 生物合成具有积极作用。然而,对 AUR 和 DON 基因启动子染色质组蛋白修饰的分析表明,在 Hep1 缺失菌株中,H3K9me3 异染色质标记强烈减少。这一发现以及 DON 基因簇侧翼基因的上调表明,HEP1 直接和间接地抑制了 DON 生物合成基因簇的表达。本研究的结果表明,染色质修饰和组成型异染色质的形成在真菌中存在一种保守的次生代谢物(SM)生物合成调控模式。