Crosstalk between the Ino80 complex and TOR signaling drives fungal adaptation to hypoxia through chromatin remodeling

ABSTRACT: In the present study, we undertook a genetic screen of the GRACE (Gene Replacement and Conditional Expression) collection to identify genes required for hypoxic (5% O2) adaptation. Through this comprehensive screen, we identified many genes spanning diverse functional categories that are required for optimal growth under hypoxia, revealing new pathways likely involved in O2 sensing, signaling, and adaptation to O2 depletion. We identified two subunits of the Ino80 chromatin-remodeling complex and one subunit of the TOR (Target Of Rapamycin) pathway as critical for sustaining fungal growth under O2-depleted conditions. Integration of ino80 mutant transcriptomic data with Ino80 DNA-binding and nucleosome-occupancy profiles under conditional INO80 depletion revealed that this chromatin remodeler controls the cellular phosphate demand accompanying hypoxic adaptation. The similarity between chromatin accessibility changes upon TOR inhibition and INO80 depletion suggests that Ino80 functions in concert with the TOR pathway to promote growth and maintain phosphate homeostasis under O2-limiting conditions. These findings provide new insight into how nutrient and O2 signaling converge on chromatin remodeling mechanisms, offering a foundation for understanding the regulatory logic that underlies hypoxic adaptation in pathogenic fungi.

ORGANISM(S): Candida albicans

PROVIDER: GSE314174 | GEO | 2025/12/22

REPOSITORIES: GEO