COMPASS复合物通过真菌病原体中的组蛋白串扰调节真菌发育和毒力。

The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen .

作者信息

Liu Ruoyan, Chen Xiaoyu, Zhao Fujie, Jiang Yixuan, Lu Zhenguo, Ji Huining, Feng Yuanyuan, Li Junqiang, Zhang Heng, Zheng Jianting, Zhang Jing, Zhao Youbao

机构信息

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

J Fungi (Basel). 2023 Jun 14;9(6):672. doi: 10.3390/jof9060672.

The Complex of Proteins Associated with Set1 (COMPASS) methylates lysine K4 on histone H3 (H3K4) and is conserved from yeast to humans. Its subunits and regulatory roles in the meningitis-causing fungal pathogen remain unknown. Here we identified the core subunits of the COMPASS complex in and and confirmed their conserved roles in H3K4 methylation. Through AlphaFold modeling, we found that Set1, Bre2, Swd1, and Swd3 form the catalytic core of the COMPASS complex and regulate the cryptococcal yeast-to-hypha transition, thermal tolerance, and virulence. The COMPASS complex-mediated histone H3K4 methylation requires H2B mono-ubiquitination by Rad6/Bre1 and the Paf1 complex in order to activate the expression of genes specific for the yeast-to-hypha transition in . Taken together, our findings demonstrate that putative COMPASS subunits function as a unified complex, contributing to cryptococcal development and virulence.

与Set1相关的蛋白质复合物（COMPASS）可使组蛋白H3上的赖氨酸K4（H3K4）发生甲基化，并且从酵母到人类都具有保守性。其亚基及其在引起脑膜炎的真菌病原体中的调控作用尚不清楚。在这里，我们在[具体物种1]和[具体物种2]中鉴定出了COMPASS复合物的核心亚基，并证实了它们在H3K4甲基化中的保守作用。通过AlphaFold建模，我们发现Set1、Bre2、Swd1和Swd3形成了COMPASS复合物的催化核心，并调节隐球菌从酵母到菌丝的转变、耐热性和毒力。COMPASS复合物介导的组蛋白H3K4甲基化需要Rad6/Bre1和Paf1复合物对H2B进行单泛素化，以便激活[具体物种]中酵母到菌丝转变特异性基因的表达。综上所述，我们的研究结果表明，假定的COMPASS亚基作为一个统一的复合物发挥作用，有助于隐球菌的发育和毒力。