The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i>
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 <i>Cryptococcus neoformans</i> remain unknown. Here we identified the core s...
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MDPI AG
2023-06-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/6/672 |
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| author | Ruoyan Liu Xiaoyu Chen Fujie Zhao Yixuan Jiang Zhenguo Lu Huining Ji Yuanyuan Feng Junqiang Li Heng Zhang Jianting Zheng Jing Zhang Youbao Zhao |
| author_facet | Ruoyan Liu Xiaoyu Chen Fujie Zhao Yixuan Jiang Zhenguo Lu Huining Ji Yuanyuan Feng Junqiang Li Heng Zhang Jianting Zheng Jing Zhang Youbao Zhao |
| author_sort | Ruoyan Liu |
| collection | DOAJ |
| description | 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 <i>Cryptococcus neoformans</i> remain unknown. Here we identified the core subunits of the COMPASS complex in <i>C. neoformans</i> and <i>C. deneoformans</i> 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 <i>C. deneoformans</i>. Taken together, our findings demonstrate that putative COMPASS subunits function as a unified complex, contributing to cryptococcal development and virulence. |
| first_indexed | 2024-03-11T02:16:51Z |
| format | Article |
| id | doaj.art-dac05a0108604ef99c876203de43d156 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-11T02:16:51Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-dac05a0108604ef99c876203de43d1562023-11-18T11:09:14ZengMDPI AGJournal of Fungi2309-608X2023-06-019667210.3390/jof9060672The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i>Ruoyan Liu0Xiaoyu Chen1Fujie Zhao2Yixuan Jiang3Zhenguo Lu4Huining Ji5Yuanyuan Feng6Junqiang Li7Heng Zhang8Jianting Zheng9Jing Zhang10Youbao Zhao11College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaThe 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 <i>Cryptococcus neoformans</i> remain unknown. Here we identified the core subunits of the COMPASS complex in <i>C. neoformans</i> and <i>C. deneoformans</i> 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 <i>C. deneoformans</i>. Taken together, our findings demonstrate that putative COMPASS subunits function as a unified complex, contributing to cryptococcal development and virulence.https://www.mdpi.com/2309-608X/9/6/672COMPASSH3K4 methylationH2B ubiquitination<i>Cryptococcus neoformans</i>yeast-to-hypha transitionvirulence |
| spellingShingle | Ruoyan Liu Xiaoyu Chen Fujie Zhao Yixuan Jiang Zhenguo Lu Huining Ji Yuanyuan Feng Junqiang Li Heng Zhang Jianting Zheng Jing Zhang Youbao Zhao The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i> Journal of Fungi COMPASS H3K4 methylation H2B ubiquitination <i>Cryptococcus neoformans</i> yeast-to-hypha transition virulence |
| title | The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i> |
| title_full | The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i> |
| title_fullStr | The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i> |
| title_full_unstemmed | The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i> |
| title_short | The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen <i>Cryptococcus neoformans</i> |
| title_sort | compass complex regulates fungal development and virulence through histone crosstalk in the fungal pathogen i cryptococcus neoformans i |
| topic | COMPASS H3K4 methylation H2B ubiquitination <i>Cryptococcus neoformans</i> yeast-to-hypha transition virulence |
| url | https://www.mdpi.com/2309-608X/9/6/672 |
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