Homeodomain protein Sxi1α independently controls cell-cell fusion and gene expression during sexual reproduction in <i>Cryptococcus deneoformans</i>
Notice bibliographique
Résumé
Abstract Sex-specific homeodomain (HD) proteins are key regulators of cell identity and sexual development in fungi, typically functioning as heterodimers to govern transcription. In the human fungal pathogens Cryptococcus neoformans and Cryptococcus deneoformans , the HD proteins Sxi1α and Sxi2 a (Sex-inducer 1α and 2 a ) have been characterized as interacting components that play critical roles in sexual development during α x a sexual reproduction. α cells are the predominant mating type in natural populations of Cryptococcus , and unisexual (same-sex) mating can also occur in certain genetic backgrounds. The roles of Sxi1α and Sxi2 a in unisexual reproduction are not fully understood. To elucidate the functions of Sxi1α and Sxi2 a , we first applied AlphaFold3 prediction, which identified potential heterodimeric and homodimeric complexes. Formation of a Sxi2 a homodimer was then experimentally validated through yeast two-hybrid assays. We subsequently deleted SXI1 α and SXI2 a in the hyper-filamentous self-fertile C. deneoformans strains XL280α and XL280 a . Disruption of these genes did not result in noticeable defects in vegetative growth, virulence-associated traits, colony morphology, sporulation, or competitive fitness during unisexual crosses. Interestingly, both bilateral (mutant x mutant) and unilateral (mutant x wildtype) crosses involving the sxi1 αΔ mutant significantly increased α-α cell fusion efficiency, suggesting a previously unrecognized inhibitory role for Sxi1α in regulating same-sex cell fusion. Consistently, genes encoding mating pheromones and the α-pheromone receptor Ste3 were upregulated in the sxi1 αΔ fusion assays. Transcriptomic analysis of sxi1 αΔ and sxi2 a Δ mutants led to the identification of unique subsets of genes negatively regulated by each transcription factor during unisexual reproduction. Additionally, α x a crosses between null mutants of sxi1 αΔ and sxi2 a Δ revealed differential regulation of mating-type ( MAT ) loci genes dependent only on Sxi1α or Sxi2 a . Together, our findings reveal a novel role for Sxi1α in governing cell fusion and demonstrate that Sxi1α and Sxi2 a have distinct transcriptional control during unisexual and α x a sexual reproduction, potentially exerting opposing regulation of sex-specific MAT genes. Author Summary Analogous to processes observed in many eukaryotic organisms, fungal sexual reproduction reshuffles genetic material, producing novel genetic variants with increased fitness and/or adaptive potential. The human fungal pathogen Cryptococcus deneoformans is widespread in the environment and can cause severe infections in immunocompromised individuals. Sexual reproduction in this species occurs between cells of either opposite mating types (α x a mating) or the same mating type (α x α and a x a unisexual reproduction). The mating type-specific homeodomain transcription factors Sxi1α and Sxi2 a are known to form a complex that broadly controls sexual development following α and a cell fusion. Here, we find that Sxi1α inhibits cell-cell fusion during unisexual reproduction, while its partner, Sxi2 a , shows only limited inhibition in certain genetic contexts. Further, we show that Sxi1α and Sxi2 a regulate transcription of distinct gene sets during both α x a and unisexual reproduction, including many within the mating-type ( MAT ) loci, often in opposing manners. Together, these findings reveal that Sxi1α and Sxi2 a function both cooperatively and independently, thereby allowing for a more flexible and finely-tuned mating control system than previously recognized, providing insight into how this organism generates genetic variation and adapts to changing environments.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».