bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.05.15.654408

Polycomb repressive complex 2 regulates sexual development in Neurospora crassa

Deaven, A. M.·Ameri-Solanky, A. J.·Lewis, Z. A.
View original source ↗Export metadata ↓

Abstract

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 broadly and uniquely 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 activation of both PRC2-methylated and unmethylated DIGs, showing evidence of a transcriptional reprogramming event. Together, these data suggest that PRC2 is part of a developmental checkpoint that restricts fruiting body development to the appropriate conditions.

Source connections

Explore related subjects

geneticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Deaven, A. M., Ameri-Solanky, A. J., Lewis, Z. A.. 2025-05-16. Polycomb repressive complex 2 regulates sexual development in Neurospora crassa. https://doi.org/10.1101/2025.05.15.654408

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD

Progressive hepatic fibrosis is the principal determinant of morbidity and mortality in metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD/MASH). Mitochondrial dysfunction is a hallmark of MASH, and the release of mitochondrial damage-associated molecular patterns (mito-DAMPs) from injured hepatocytes can promote fibrosis. However, how mitochondrial dynamics and quality control shape the fibrotic response in MASLD/MASH remains unclear. Here, through large-scale genomic analyses of mitochondrial genes governing mitophagy, fusion and fission in human MASLD, with a power-equivalent sample size of approximately 700,000 individuals, we identify a strong association between hepatic fibrosis and the mitochondrial fusion factor dynamin-like GTPase optic atrophy 1 (OPA1). OPA1 transcripts and protein abundance in the liver epithelium were progressively dysregulated with advancing fibrosis. In mice, hepatocyte-specific OPA1 loss alone was sufficient to induce hepatic stellate cell activation and fibrosis in zone 3, promoted the release of mito-DAMPs into the circulation and exacerbated fibrosis in experimental MASH. These findings identify OPA1 as a central regulator of the hepatic fibrotic response and connect defective mitochondrial homeostasis to mito-DAMP release, hepatic stellate cell activation and fibrosis in MASLD.

genetics↗
bioRxiv2026

Temporal control of mitochondrial mutagenesis reveals the fate of mtDNA mutations with age

Mutations in the mitochondrial genome (mtDNA) play a critical role in the aging process and a wide variety of age-related diseases. However, it remains unclear when the mutations that drive physiological decline arise. To answer this question, we generated a new mouse model in which mitochondrial mutagenesis can be confined to a defined window of time. Surprisingly, we found that mutations that arise during the first two months of life are sufficient to drive a wide variety of age-related pathologies, and that the severity of this pathology is broadly regulated by distinct, tissue-specific selective pressures that control the fate of mtDNA mutations with age. Further, we found that selection against deleterious variants can be modulated by manipulation of mitochondrial fusion in vitro and in vivo. These observations raise the possibility that in some tissues, the pace of aging is pre-determined by events that occur early in life and that interventions targeting mitochondrial fusion may be able to slow down or reverse the expansion of these pathogenic variants. These results carry far-reaching implications for strategies aimed at preventing or delaying age-related decline.

genetics↗
bioRxiv2026

Innate immune stress pathway activation underlies heterochromatin dysfunction pathology

Heterochromatin loss disrupts nuclear architecture, gene regulation and repetitive element silencing, and is associated with diverse human diseases. However, mechanisms linking heterochromatin dysfunction to pathological phenotypes remain unclear. Using genetic interaction screening and genomic analyses in C. elegans, we identify secondary activation of the Intracellular Pathogen Response (IPR), an innate immune stress pathway, as a major contributor to heterochromatin mutant phenotypes. Constitutive IPR activation phenocopies slow growth and indirect transcriptional changes observed in these mutants. Depletion of genetic enhancers further increased, whereas suppressor RNAi attenuated IPR activation, with direct heterochromatin targets remaining substantially deregulated. Notably, many suppressors encode active chromatin components, and mild reduction of RNA polymerase II activity ameliorates growth defects in C. elegans HP1 mutants and human HP1-deficient cells. Our findings reveal secondary stress response activation as an important mechanism linking heterochromatin dysfunction to pathology and identify transcriptional dampening as a potential therapeutic strategy for mitigating these effects.

genetics↗