Histone acetyltransferase Gcn5-mediated histone H3 acetylation facilitates cryptococcal morphogenesis and sexual reproduction

作者：Man Chen, Yuanli Liu, Zhuoda Liu, Lin Su, Lili Yan, Yuan Huang, Ye Huang, Wei Zhang, Xinping Xu, Fanglin Zheng · 发表于：mSphere · 年份：2023 · DOI：10.1128/msphere.00299-23 · 被引用次数：12 · 研究领域：Fungal Infections and Studies、Yeasts and Rust Fungi Studies、Plant Pathogens and Fungal Diseases

ABSTRACT Sexual reproduction is the primary driving force behind eukaryotic environmental adaptation and evolution. In the human fungal pathogen Cryptococcus neoformans , sexual reproduction plays a critical role in the emergence of highly virulent strains and drug-resistant variants. The sexual life cycle of C. neoformans commences with the yeast-hyphae transition in response to mating stimulation, followed by hyphal extension and further differentiation into basidium, where meiosis takes place to produce basidiospore. Although extensive studies have been conducted on the determining factors and genetic pathways involved in the sexual cycle, the precise contribution of epigenetic modifications in this process remains elusive. Here, through a systematic genetic screening assay, we find that Gcn5 is the specific histone acetyltransferase involved in yeast-hyphae morphogenesis in C. neoformans . Furthermore, we demonstrate that Gcn5 is indispensable for completing the entire sexual cycle of C. neoformans , including yeast-hyphae transition, hyphal development, basidium differentiation, meiosis, and subsequent sporulation. Additionally, chromatin immunoprecipitation assay demonstrates that Gcn5-mediated H3K14ac modification is closely associated with the activated transcription of master transcriptional regulator gene ZNF2 and its downstream targets under mating-inducing condition. Moreover, disruption of two additional subunits encoding gene within the SAGA complex, ADA3 and SP...