Abstract：
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.
摘要：
ATP依赖性染色质重塑复合物在许多重要的细胞过程中发挥重要作用。包括转录调节，DNA复制,和修复。驱逐H2A。Z,组蛋白H2A的变体,在白色念珠菌中菌丝形成需要菌丝特异性基因的启动子。然而,调节H2A的机制。菌丝形成过程中的Z去除仍然未知。在这项研究中,我们证明了INO80，INO80复合物的核心催化亚基，在菌丝诱导过程中以Arp8依赖性方式募集到菌丝特异性启动子，并促进了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（HSGs）的表达和菌丝发育。此外,我们发现Ino80对小鼠全身感染期间白色念珠菌的毒力至关重要。有趣的是,Arp5，一种INO80复合物特异性成分，在DNA损伤反应期间与Ino80协同作用，但对于菌丝诱导是不必要的。我们的发现澄清了Ino80对菌丝发育至关重要，DNA损伤反应,白色念珠菌的发病机制。
