Polycomb repressive complex 2 regulates sexual development in Neurospora crassa

In most branches of the fungal kingdom, sexual development marks a dramatic shift from simple multicellular hyphae to complex fruiting bodies composed of multiple tissues and cell types. It is essential to tightly regulate development to prevent unnecessary energy investment into building these structures. Polycomb repressive complex 2 (PRC2) is a highly conserved regulator of development in multicellular organisms. In plants, animals, and some fungi, PRC2 tri-methylates histone H3 lysine 27 in promoters and gene bodies to repress gene expression. In Neurospora crassa, H3K27me3-associated genes are poorly conserved and stably repressed in standard lab conditions. Through analysis of publicly available RNA-seq experiments, we found that PRC2-methylated genes are specifically activated during sexual development. PRC2-methylated genes comprise a distinct subset of developmentally induced genes (DIGs) characterized by an exceptionally high degree of cell-type specificity. Loss of PRC2 activity results in the precocious formation of perithecia-like structures (dubbed false perithecia), even in the absence of a compatible mating-type partner. These structures show a unique gene expression profile with the activation of both PRC2-methylated and unmethylated DIGs, suggesting that loss of PRC2 leads to a major transcriptional reprogramming event. Together, these data suggest that PRC2 is part of a developmental checkpoint that restricts fruiting body development to the appropriate conditions.IMPORTANCEDevelopment of multicellular eukaryotes involves transcriptional reprogramming to drive cell fate transitions. This study identified PRC2 as a critical regulator of cell fate in the model filamentous fungus Neurospora crassa, where it silences a subset of sexual development genes. Loss of regulation by PRC2 triggers a major reprogramming event in which genes specifying sexual tissues cannot be repressed, causing a homeotic transition. These results provide novel insights into the role of PRC2-mediated regulation in the fungal kingdom and uncover a critical checkpoint regulating complex multicellular development.