{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:08:28Z","timestamp":1788458908666,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012084","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000}}],"reference-count":83,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["AI039115-28"],"award-info":[{"award-number":["AI039115-28"]}]},{"name":"NIH\/NIAID","award":["AI050113-20"],"award-info":[{"award-number":["AI050113-20"]}]},{"name":"NIH\/NIAID","award":["AI133654-07"],"award-info":[{"award-number":["AI133654-07"]}]},{"DOI":"10.13039\/100007631","name":"Canadian Institute for Advanced Research","doi-asserted-by":"crossref","award":["Fungal Kingdom: Threats & Opportunities"],"award-info":[{"award-number":["Fungal Kingdom: Threats & Opportunities"]}],"id":[{"id":"10.13039\/100007631","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    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\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    and\n                    <jats:italic>Cryptococcus deneoformans<\/jats:italic>\n                    , the HD proteins Sxi1\u03b1 and Sxi2\n                    <jats:bold>a<\/jats:bold>\n                    (Sex-inducer 1\u03b1 and 2\n                    <jats:bold>a<\/jats:bold>\n                    ) have been characterized as interacting components that play critical roles in sexual development during \u03b1 x\n                    <jats:bold>a<\/jats:bold>\n                    sexual reproduction. \u03b1 cells are the predominant mating type in natural populations of\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    , and unisexual (same-sex) mating can also occur in certain genetic backgrounds. The roles of Sxi1\u03b1 and Sxi2\n                    <jats:bold>a<\/jats:bold>\n                    in unisexual reproduction are not fully understood. To elucidate the functions of Sxi1\u03b1 and Sxi2\n                    <jats:bold>a<\/jats:bold>\n                    , we first applied AlphaFold3 prediction, which identified potential heterodimeric and homodimeric complexes. Formation of a Sxi2\n                    <jats:bold>a<\/jats:bold>\n                    homodimer was then experimentally validated through yeast two-hybrid assays. We subsequently deleted\n                    <jats:italic>SXI1<\/jats:italic>\n                    \u03b1 and\n                    <jats:italic>SXI2<\/jats:italic>\n                    <jats:bold>a<\/jats:bold>\n                    in the hyper-filamentous self-fertile\n                    <jats:italic>C. deneoformans<\/jats:italic>\n                    strains XL280\u03b1 and XL280\n                    <jats:bold>a<\/jats:bold>\n                    . 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 wild type) crosses involving the\n                    <jats:italic>sxi1<\/jats:italic>\n                    \u03b1\u0394 mutant showed significantly increased \u03b1-\u03b1 cell fusion efficiency, suggesting a previously unrecognized inhibitory role for Sxi1\u03b1 in regulating same-sex cell fusion. Consistently, genes encoding mating pheromones and the \u03b1-pheromone receptor Ste3 were upregulated in the\n                    <jats:italic>sxi1<\/jats:italic>\n                    \u03b1\u0394 fusion assays. Transcriptomic analysis of\n                    <jats:italic>sxi1<\/jats:italic>\n                    \u03b1\u0394 and\n                    <jats:italic>sxi2<\/jats:italic>\n                    <jats:bold>a<\/jats:bold>\n                    \u0394 mutants led to the identification of unique subsets of genes negatively regulated by each transcription factor during unisexual reproduction. Additionally, \u03b1 x\n                    <jats:bold>a<\/jats:bold>\n                    crosses between\n                    <jats:italic>sxi1<\/jats:italic>\n                    \u03b1\u0394 and\n                    <jats:italic>sxi2<\/jats:italic>\n                    <jats:bold>a<\/jats:bold>\n                    \u0394 mutants revealed differential regulation of mating-type (\n                    <jats:italic>MAT<\/jats:italic>\n                    ) loci genes dependent only on Sxi1\u03b1 or Sxi2\n                    <jats:bold>a<\/jats:bold>\n                    . Together, our findings reveal a novel role for Sxi1\u03b1 in governing cell fusion and demonstrate that Sxi1\u03b1 and Sxi2\n                    <jats:bold>a<\/jats:bold>\n                    have distinct transcriptional control during unisexual and \u03b1 x\n                    <jats:bold>a<\/jats:bold>\n                    sexual reproduction, potentially exerting opposing regulation of sex-specific\n                    <jats:italic>MAT<\/jats:italic>\n                    genes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012084","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:33:24Z","timestamp":1773336804000},"page":"e1012084","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Homeodomain protein Sxi1\u03b1 independently controls cell-cell fusion and gene expression during sexual reproduction in Cryptococcus deneoformans"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-0926","authenticated-orcid":true,"given":"Jun","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8544-9292","authenticated-orcid":true,"given":"Anna E.","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-1045","authenticated-orcid":true,"given":"Patricia P.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6420-0976","authenticated-orcid":true,"given":"Liping","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6369-5995","authenticated-orcid":true,"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"pgen.1012084.ref001","volume":"23","author":"MA 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