State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Mol Microbiol. 2022 Jul;118(1-2):92-104. doi: 10.1111/mmi.14954. Epub 2022 Jun 28.
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.
ATP 依赖的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，包括转录调控、DNA 复制和修复。在白色念珠菌中，从菌丝特异性基因的启动子中驱逐组蛋白 H2A 的变体 H2A.Z 对于菌丝形成是必需的。然而，调节菌丝形成过程中 H2A.Z 去除的机制尚不清楚。在这项研究中，我们证明了 INO80 复合物的核心催化亚基 Ino80 在 Arp8 依赖的方式下被招募到菌丝特异性启动子，从而促进 H2A.Z 的去除。删除 INO80 或突变 Ino80 的 ATP 酶位点会损害菌丝特异性基因 (HSGs) 的表达和菌丝的发育。此外，我们表明，Ino80 对于白色念珠菌在小鼠全身性感染期间的毒力是必需的。有趣的是，Arp5，一种 INO80 复合物特异性成分，在 DNA 损伤反应中与 Ino80 协同作用，但对于菌丝诱导是可有可无的。我们的研究结果表明，Ino80 对于白色念珠菌的菌丝发育、DNA 损伤反应和发病机制至关重要。
