ATP-dependent chromatin remodeling complexes play important roles in many essential cellular processes, including transcription regulation, DNA replication, and repair. Evicting H2A.Z, a variant of histone H2A, from the promoter of hypha-specific genes is required for hyphal formation in Candida albicans. However, the mechanism that regulates H2A.Z removal during hyphal formation remains unknown. In this study, we demonstrated that Ino80, the core catalytic subunit of the INO80 complex, was recruited to hypha-specific promoters during hyphal induction in Arp8 dependent manner and facilitated the removal of H2A.Z. Deleting INO80 or mutating the ATPase site of Ino80 impairs the expression of hypha-specific genes (HSGs) and hyphal development. In addition, we showed that Ino80 was essential for the virulence of C. albicans during systemic infections in mice. Interestingly, Arp5, an INO80 complex-specific component, acts in concert with Ino80 during DNA damage responses but is dispensable for hyphal induction. Our findings clarified that Ino80 was critical for hyphal development, DNA damage response, and pathogenesis in C. albicans.

中文翻译：

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Ino80 是 H2A.Z 从菌丝特异性启动子驱逐和白色念珠菌菌丝发育所必需的

ATP 依赖性染色质重塑复合物在许多基本细胞过程中发挥重要作用，包括转录调节、DNA 复制和修复。白色念珠菌的菌丝形成需要从菌丝特异性基因的启动子中去除组蛋白 H2A 的变体 H2A.Z。然而，在菌丝形成过程中调节 H2A.Z 去除的机制仍然未知。在这项研究中，我们证明了 INO80 复合物的核心催化亚基 Ino80 在菌丝诱导期间以 Arp8 依赖性方式被招募到菌丝特异性启动子，并促进 H2A.Z 的去除。删除INO80或突变 Ino80 的 ATPase 位点会损害菌丝特异性基因 (HSG) 的表达和菌丝发育。此外，我们发现 Ino80在小鼠全身感染期间对白色念珠菌的毒力至关重要。有趣的是，Arp5 是一种 INO80 复合物特异性成分，在 DNA 损伤反应过程中与 Ino80 协同作用，但对于菌丝诱导是可有可无的。我们的研究结果澄清了 Ino80 对白色念珠菌的菌丝发育、DNA 损伤反应和发病机制至关重要。