
Cryptococcus neoformans, the causative agent of cryptococcosis and a representative of the Basidiomycota phylum of Fungi, is a valuable model for our understanding of eukaryotic/fungal biology. Negative feedback is a well-documented mechanism across Eukarya to regulate developmental transitions. Here, we describe a repressor of the yeast-to-hypha transition, Ref1, which completes a negative feedback loop driven by the master regulator of hyphal morphogenesis, Znf2, during sexual development. Alternative transcription of Ref1, driven by Znf2, produces a functionally distinct Ref1 isoform. Isoform-specific capacity for phase separation imparts this functional distinction, making Ref1 a stronger repressor and more vulnerable to proteolytic degradation. The multimodal nature of Ref1 provides versatility that allows cells to fine-tune Ref1 activity to suit developmental context. This work reveals a mechanism by which phase separation allows a transcriptional program to tailor its own repression to guide an organism through morphological transition.
Fungal Proteins, Phase Separation, Gene Expression Regulation, Fungal, Morphogenesis, Cryptococcus neoformans, Hyphae, Protein Isoforms, Article
Fungal Proteins, Phase Separation, Gene Expression Regulation, Fungal, Morphogenesis, Cryptococcus neoformans, Hyphae, Protein Isoforms, Article
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