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.
Mol Microbiol. 2021 Feb;115(2):332-343. doi: 10.1111/mmi.14619. Epub 2020 Oct 16.
The reversible yeast-hyphae transition of the human fungal pathogen Candida albicans is tightly linked to its pathogenicity. In this study, we show that histone H2B mono-ubiquitination (H2Bub) at lysine 123 was maintained at a low level in the yeast state, whereas it increased significantly during yeast-to-hyphae transition and decreased when hyphae converted to yeast. The increased H2Bub level is correlated with activation of the hyphal program. H2B ubiquitination and deubiquitination are dynamically regulated by the E3 ligase Bre1 and the deubiquitinase Ubp8 during the reversible yeast-hyphae transition. The functions of Bre1 and Ubp8 in hypha-specific gene (HSG) regulation appears to be direct because both are recruited to the coding regions of HSGs during hyphal induction. The sequential recruitment of Bre1 and Ubp8 to HSGs coding regions is important for the initiation and maintenance of HSG expression. Additionally, Ubp8 contributes to the pathogenicity of C. albicans during early infection in a mouse model. Our study is the first to link H2B ubiquitination to the morphological plasticity and pathogenicity of the human fungal pathogen C. albicans and shed light on potential antifungal treatments.
人源真菌病原体白色念珠菌的可逆酵母-菌丝过渡与它的致病性紧密相关。在本研究中，我们表明组蛋白 H2B 赖氨酸 123 上的单泛素化（H2Bub）在酵母状态下保持在低水平，而在酵母到菌丝的过渡过程中显著增加，并在菌丝转化为酵母时减少。增加的 H2Bub 水平与菌丝程序的激活相关。在可逆酵母-菌丝过渡过程中，E3 连接酶 Bre1 和去泛素酶 Ubp8 动态调节 H2B 的泛素化和去泛素化。Bre1 和 Ubp8 在菌丝特异性基因（HSG）调控中的功能似乎是直接的，因为在菌丝诱导过程中，两者都被招募到 HSG 的编码区域。Bre1 和 Ubp8 到 HSG 编码区域的顺序招募对于 HSG 表达的起始和维持很重要。此外，Ubp8 在小鼠模型中白色念珠菌早期感染期间有助于其致病性。我们的研究首次将 H2B 泛素化与人类真菌病原体白色念珠菌的形态可塑性和致病性联系起来，并为潜在的抗真菌治疗提供了线索。
