Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite- and same-sex mating in Cryptococcus neoformans.
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.
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https://hdl.handle.net/10161/4468Published Version (Please cite this version)
10.1371/journal.pgen.1000953Publication Info
Lin, Xiaorong; Jackson, Jennifer C; Feretzaki, Marianna; Xue, Chaoyang; & Heitman,
Joseph (2010). Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite-
and same-sex mating in Cryptococcus neoformans. PLoS genetics, 6(5). pp. e1000953. 10.1371/journal.pgen.1000953. Retrieved from https://hdl.handle.net/10161/4468.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joseph Heitman
Chair, Department of Molecular Genetics and Microbiology
Joseph Heitman was an undergraduate at the University of Chicago (1980-1984), graduating
from the BS-MS program with dual degrees in chemistry and biochemistry with general
and special honors. He then matriculated as an MD-PhD student at Cornell and Rockefeller
Universities and worked with Peter Model and Norton Zinder on how restriction enzymes
recognize specific DNA sequences and how bacteria respond to and repair DNA breaks
and nicks. Dr. Heitman moved as an EMBO long-term fellow to the Bi

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