Journal
MOLECULAR MICROBIOLOGY
Volume 72, Issue 6, Pages 1334-1347Publisher
WILEY
DOI: 10.1111/j.1365-2958.2009.06719.x
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Funding
- NIH [R01 AI064287, R01 G069420, S10 RR13790]
- Burroughs Wellcome Fund Career Award in the Biomedical Sciences
- NSF [BIR-9512577]
- University of Wisconsin, Madison
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR013790] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI064287] Funding Source: NIH RePORTER
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P>Homeodomain proteins function in fungi to specify cell types and control sexual development. In the meningoencephalitis-causing fungal pathogen Cryptococcus neoformans, sexual development leads to the production of spores (suspected infectious particles). Sexual development is controlled by the homeodomain transcription factors Sxi1 alpha and Sxi2a, but the mechanism by which they act is unknown. To understand how the Sxi proteins regulate development, we characterized their binding properties in vitro, showing that Sxi2a does not require a partner to bind DNA with high affinity. We then utilized a novel approach, Cognate Site Identifier (CSI) arrays, to define a comprehensive DNA-binding profile for Sxi2a, revealing a consensus sequence distinct from those of other fungal homeodomain proteins. Finally, we show that the homeodomains of both Sxi proteins are required for sexual development, a departure from related fungi. Our findings support a model in which Sxi1 alpha and Sxi2a control sexual development in a homeodomain-dependent manner by binding to DNA sequences that differ from those defined in previously established fungal paradigms.
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