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Targets of the S ex I nducer homeodomain proteins are required for fungal development and virulence in C ryptococcus neoformans
Author(s) -
Mead Matthew E.,
Stanton Brynne C.,
Kruzel Emilia K.,
Hull Christina M.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12898
Subject(s) - biology , homeobox , virulence , gene , transcription factor , genetics , in silico , transcription (linguistics) , genome , transcriptional regulation , fungal protein , saccharomyces cerevisiae , linguistics , philosophy
Summary In the yeast S accharomyces cerevisiae , the regulation of cell types by homeodomain transcription factors is a key paradigm; however, many questions remain regarding this class of developmental regulators in other fungi. In the human fungal pathogen C ryptococcus neoformans , the homeodomain transcription factors S xi1α and S xi2 a are required for sexual development that produces infectious spores, but the molecular mechanisms by which they drive this process are unknown. To better understand homeodomain control of fungal development, we determined the targets of the S xi2 a ‐ S xi1α heterodimer using whole genome expression analyses paired with in silico and in vitro binding site identification methods. We identified S xi‐regulated genes that contained a site bound directly by the S xi proteins that is required for full regulation in vivo. Among the targets of the S xi2 a ‐ S xi1α complex were many genes known to be involved in sexual reproduction, as well as several well‐studied virulence genes. Our findings suggest that genes involved in sexual development are also important in mammalian disease. Our work advances the understanding of how homeodomain transcription factors control complex developmental events and suggests an intimate link between fungal development and virulence.