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

Ruoyan Liu1, Xiaoyu Chen1, Fujie Zhao1

  • 1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.

Insights

Researchers identified the core subunits of the Complex of Proteins Associated with Set1 (COMPASS) in the fungal pathogen Cryptococcus neoformans. This complex is crucial for histone methylation, regulating fungal development and virulence.

Area of Science:

  • Molecular Biology
  • Mycology
  • Epigenetics

Background:

  • The Complex of Proteins Associated with Set1 (COMPASS) is a conserved epigenetic regulator involved in histone methylation.
  • Its function and composition in the fungal pathogen *Cryptococcus neoformans* are largely unknown.
  • Understanding COMPASS in *C. neoformans* is critical for deciphering fungal development and pathogenesis.

Purpose of the Study:

  • To identify the core subunits of the COMPASS complex in *Cryptococcus neoformans* and *C. deneoformans*.
  • To elucidate the regulatory roles of COMPASS in cryptococcal development and virulence.
  • To investigate the mechanism of COMPASS-mediated histone methylation in *C. neoformans*.

Main Methods:

  • Subunit identification and complex assembly analysis.
  • AlphaFold protein structure prediction for COMPASS subunits.
  • Histone methylation assays and gene expression analysis.
  • Functional assays for cryptococcal development and virulence.

Main Results:

  • Core COMPASS subunits (Set1, Bre2, Swd1, Swd3) were identified and confirmed in *C. neoformans* and *C. deneoformans*.
  • AlphaFold modeling revealed the catalytic core of the COMPASS complex.
  • COMPASS regulates the yeast-to-hypha transition, thermal tolerance, and virulence in *C. neoformans*.
  • Histone H3K4 methylation by COMPASS requires H2B monoubiquitination and the Paf1 complex.

Conclusions:

  • The identified COMPASS subunits form a functional complex in *C. neoformans*.
  • COMPASS plays a conserved role in H3K4 methylation, impacting cryptococcal development and virulence.
  • This study provides insights into the epigenetic regulation of fungal pathogenesis.

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