Ino80 is required for H2A.Z eviction from hypha-specific promoters and hyphal development of Candida albicans.

Ino80 is required for H2A.Z eviction from hypha-specific promoters and hyphal development of Candida albicans.
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DOI:
10.1111/mmi.14954
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发表时间:
2022-07
影响因子:
3.6
通讯作者:
Chen, Jiangye
Chen, Jiangye
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao, Qun;Dai, Baodi;Wu, Hongyu;Zhu, Wencheng;Chen, Jiangye

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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,包括转录调控,DNA复制和修复。从菌丝特异性基因的启动子中驱逐H2A.Z(组蛋白H2A的变体)是白色念珠菌中菌丝形成所必需的。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INO 80或突变Ino 80的ATP酶位点会损害菌丝特异性基因(HSG)的表达和菌丝发育。此外,我们还发现Ino80对C.在小鼠全身感染期间的白色念珠菌。有趣的是,Arp5是一种INO80复合物特异性组分,在DNA损伤反应期间与Ino80协同作用,但在菌丝诱导中不起作用。研究结果表明,Ino80基因在C.白色念珠菌INO 80和SWR 1复合物调节白念珠菌菌丝发育过程中H2 A. Z的交换在酵母状态下,SWR1复合物介导菌丝特异性启动子中的H2A. Z沉积,以抑制菌丝特异性基因的表达。在菌丝诱导过程中,SWR1复合物离开启动子,INO80复合物通过Arp8亚基被募集到这些区域。Ino80从这些启动子中驱逐H2A.Z有助于菌丝特异性基因的表达,从而促进菌丝发育。
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. INO80 and SWR1 complexes regulate the exchange of H2A.Z during hyphal development of Candida albicans. In the yeast state, the SWR1 complex mediates H2A.Z deposition in hypha‐specific promoters to inhibit the expression of hypha‐specific genes. During hyphal induction, the SWR1 complex departs from promoters, and the INO80 complex is recruited to these regions via the Arp8 subunit. Eviction of H2A.Z from these promoters by Ino80 facilitates the expression of hypha‐specific genes, thereby promoting hyphal development.
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