Cánovas David, Marcos Ana T, Gacek Agnieszka, Ramos María S, Gutiérrez Gabriel, Reyes-Domínguez Yazmid, Strauss Joseph
Departmento de Genética, Facultad de Biología, Universidad de Sevilla, 41012, Spain Fungal Genetics and Genomics Unit, Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna A-3430, Austria
Departmento de Genética, Facultad de Biología, Universidad de Sevilla, 41012, Spain.
Genetics. 2014 Aug;197(4):1175-89. doi: 10.1534/genetics.114.165688. Epub 2014 Jun 6.
Acetylation of histones is a key regulatory mechanism of gene expression in eukaryotes. GcnE is an acetyltransferase of Aspergillus nidulans involved in the acetylation of histone H3 at lysine 9 and lysine 14. Previous works have demonstrated that deletion of gcnE results in defects in primary and secondary metabolism. Here we unveil the role of GcnE in development and show that a ∆gcnE mutant strain has minor growth defects but is impaired in normal conidiophore development. No signs of conidiation were found after 3 days of incubation, and immature and aberrant conidiophores were found after 1 week of incubation. Centroid linkage clustering and principal component (PC) analysis of transcriptomic data suggest that GcnE occupies a central position in Aspergillus developmental regulation and that it is essential for inducing conidiation genes. GcnE function was found to be required for the acetylation of histone H3K9/K14 at the promoter of the master regulator of conidiation, brlA, as well as at the promoters of the upstream developmental regulators of conidiation flbA, flbB, flbC, and flbD (fluffy genes). However, analysis of the gene expression of brlA and the fluffy genes revealed that the lack of conidiation originated in a complete absence of brlA expression in the ∆gcnE strain. Ectopic induction of brlA from a heterologous alcA promoter did not remediate the conidiation defects in the ∆gcnE strain, suggesting that additional GcnE-mediated mechanisms must operate. Therefore, we conclude that GcnE is the only nonessential histone modifier with a strong role in fungal development found so far.
组蛋白乙酰化是真核生物中基因表达的关键调控机制。GcnE是构巢曲霉的一种乙酰转移酶,参与组蛋白H3赖氨酸9和赖氨酸14的乙酰化。先前的研究表明,gcnE的缺失会导致初级和次级代谢缺陷。在此,我们揭示了GcnE在发育中的作用,并表明∆gcnE突变菌株有轻微的生长缺陷,但在正常分生孢子梗发育方面受损。培养3天后未发现分生孢子形成的迹象,培养1周后发现不成熟和异常的分生孢子梗。转录组数据的质心连锁聚类和主成分(PC)分析表明,GcnE在曲霉发育调控中占据中心位置,并且它对于诱导分生孢子形成基因至关重要。发现GcnE功能对于分生孢子形成的主要调节因子brlA启动子以及分生孢子形成上游发育调节因子flbA、flbB、flbC和flbD(蓬松基因)启动子处的组蛋白H3K9/K14乙酰化是必需的。然而,对brlA和蓬松基因的基因表达分析表明,分生孢子形成的缺乏源于∆gcnE菌株中brlA表达的完全缺失。从异源alcA启动子异位诱导brlA并不能修复∆gcnE菌株中的分生孢子形成缺陷,这表明必须有其他GcnE介导的机制起作用。因此,我们得出结论,GcnE是迄今为止发现的在真菌发育中具有重要作用的唯一非必需组蛋白修饰因子。