Wang Long-Chi, Montalvo-Munoz Fernando, Tsai Yuan-Chan, Liang Chung-Yi, Chang Chun-Chuan, Lo Wan-Sheng
Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan ; Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
Institute of Plant and Microbial Biology, Academia Sinica, Taipei 115, Taiwan.
Biomed Res Int. 2015;2015:284692. doi: 10.1155/2015/284692. Epub 2015 Apr 2.
Filamentous growth is one of the key features of pathogenic fungi during the early infectious phase. The pseudohyphal development of yeast Saccharomyces cerevisiae shares similar characteristics with hyphae elongation in pathogenic fungi. The expression of FLO11 is essential for adhesive growth and filament formation in yeast and is governed by a multilayered transcriptional network. Here we discovered a role for the histone acetyltransferase general control nonderepressible 5 (Gcn5) in regulating FLO11-mediated pseudohyphal growth. The expression patterns of FLO11 were distinct in haploid and diploid yeast under amino acid starvation induced by 3-amino-1,2,4-triazole (3AT). In diploids, FLO11 expression was substantially induced at a very early stage of pseudohyphal development and decreased quickly, but in haploids, it was gradually induced. Furthermore, the transcription factor Gcn4 was recruited to the Sfl1-Flo8 toggle sites at the FLO11 promoter under 3AT treatment. Moreover, the histone acetylase activity of Gcn5 was required for FLO11 induction. Finally, Gcn5 functioned as a negative regulator of the noncoding RNA ICR1, which is known to suppress FLO11 expression. Gcn5 plays an important role in the regulatory network of FLO11 expression via Gcn4 by downregulating ICR1 expression, which derepresses FLO11 for promoting pseudohyphal development.
丝状生长是致病真菌在早期感染阶段的关键特征之一。酿酒酵母的假菌丝发育与致病真菌中的菌丝伸长具有相似的特征。FLO11的表达对于酵母中的黏附生长和丝状形成至关重要，并且受多层转录网络调控。在这里，我们发现组蛋白乙酰转移酶全面控制非抑制因子5（Gcn5）在调节FLO11介导的假菌丝生长中发挥作用。在3-氨基-1,2,4-三唑（3AT）诱导的氨基酸饥饿条件下，FLO11在单倍体和二倍体酵母中的表达模式不同。在二倍体中，FLO11表达在假菌丝发育的非常早期阶段被大量诱导并迅速下降，但在单倍体中，它是逐渐被诱导的。此外，在3AT处理下，转录因子Gcn4被招募到FLO11启动子处的Sfl1-Flo8转换位点。而且，FLO11的诱导需要Gcn5的组蛋白乙酰化酶活性。最后，Gcn5作为非编码RNA ICR1的负调节因子发挥作用，已知ICR1可抑制FLO11表达。Gcn5通过下调ICR1的表达，在经由Gcn4的FLO11表达调控网络中发挥重要作用，从而解除对FLO11的抑制以促进假菌丝发育。
