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dc.contributor.author Lin, X
dc.contributor.author Jackson, JC
dc.contributor.author Feretzaki, M
dc.contributor.author Xue, C
dc.contributor.author Heitman, J
dc.date.accessioned 2011-06-21T17:31:20Z
dc.date.issued 2010
dc.identifier.citation PLoS genetics, 2010, 6 (5), pp. e1000953 - ?
dc.identifier.issn 1553-7404
dc.identifier.uri http://hdl.handle.net/10161/4468
dc.description.abstract Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from a unicellular yeast to multicellular hyphae during opposite sex (mating) and unisexual reproduction (same-sex mating). Opposite- and same-sex mating are induced by similar environmental conditions and involve many shared components, including the conserved pheromone sensing Cpk1 MAPK signal transduction cascade that governs the dimorphic switch in C. neoformans. However, the homeodomain cell identity proteins Sxi1alpha/Sxi2a encoded by the mating type locus that are essential for completion of sexual reproduction following cell-cell fusion during opposite-sex mating are dispensable for same-sex mating. Therefore, identification of downstream targets of the Cpk1 MAPK pathway holds the key to understanding molecular mechanisms governing the two distinct developmental fates. Thus far, homology-based approaches failed to identify downstream transcription factors which may therefore be species-specific. Here, we applied insertional mutagenesis via Agrobacterium-mediated transformation and transcription analysis using whole genome microarrays to identify factors involved in C. neoformans differentiation. Two transcription factors, Mat2 and Znf2, were identified as key regulators of hyphal growth during same- and opposite-sex mating. Mat2 is an HMG domain factor, and Znf2 is a zinc finger protein; neither is encoded by the mating type locus. Genetic, phenotypic, and transcriptional analyses of Mat2 and Znf2 provide evidence that Mat2 is a downstream transcription factor of the Cpk1 MAPK pathway whereas Znf2 functions as a more terminal hyphal morphogenesis determinant. Although the components of the MAPK pathway including Mat2 are not required for virulence in animal models, Znf2, as a hyphal morphology determinant, is a negative regulator of virulence. Further characterization of these elements and their target circuits will reveal genes controlling biological processes central to fungal development and virulence.
dc.format.extent e1000953 - ?
dc.language.iso en_US en_US
dc.relation.ispartof PLoS genetics
dc.relation.isversionof 10.1371/journal.pgen.1000953
dc.title Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite- and same-sex mating in Cryptococcus neoformans.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-5-0 en_US
duke.description.endpage e1000953 en_US
duke.description.issue 5 en_US
duke.description.startpage e1000953 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Genetics en_US
pubs.issue 5
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Pharmacology & Cancer Biology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Infectious Diseases
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.volume 6

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