The COMPASS Complex Regulates Fungal Development and Virulence Through Histone Crosstalk in the Fungal Pathogen
Overview
Authors
Affiliations
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.
Rai M, Rai R Pathogens. 2025; 13(12.
PMID: 39770340 PMC: 11728789. DOI: 10.3390/pathogens13121080.
Phenotypic landscape of a fungal meningitis pathogen reveals its unique biology.
Boucher M, Banerjee S, Joshi M, Wei A, Huang M, Lei S bioRxiv. 2024; .
PMID: 39484549 PMC: 11526942. DOI: 10.1101/2024.10.22.619677.
Epigenetic Regulation of Fungal Secondary Metabolism.
Zhang Y, Yu W, Lu Y, Wu Y, Ouyang Z, Tu Y J Fungi (Basel). 2024; 10(9).
PMID: 39330408 PMC: 11433216. DOI: 10.3390/jof10090648.
Essential roles of Rad6 in conidial property, stress tolerance, and pathogenicity of .
Guan Y, He H, Guo Y, Zhang L Virulence. 2024; 15(1):2362748.
PMID: 38860453 PMC: 11174126. DOI: 10.1080/21505594.2024.2362748.
Chen M, Liu Y, Liu Z, Su L, Yan L, Huang Y mSphere. 2023; 8(6):e0029923.
PMID: 37850793 PMC: 10732044. DOI: 10.1128/msphere.00299-23.