Eukaryotic Cell
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EC Accepts, published online ahead of print on 9 November 2007
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Eukaryotic Cell doi:10.1128/EC.00377-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Sexual development in C. neoformans requires CLP1, a target of the homeodomain transcription factors Sxi1{alpha} and Sxi2a

Joanne L. Ekena, Brynne C. Stanton, Jessica A. Schiebe-Owens, and Christina M. Hull*

Department of Biomolecular Chemistry; Department of Medical Microbiology & Immunology; University of Wisconsin, School of Medicine and Public Health, Madison, WI 53706

* To whom correspondence should be addressed. Email: cmhull{at}wisc.edu.


   Abstract

Sexual development in the human fungal pathogen Cryptococcus neoformans is a multi-step process that results in the formation of spores, the likely infectious particles. A critical step in this developmental process is the transition from bud-form growth to filamentous growth. This transition is controlled by the homeodomain transcription factors Sxi1{alpha} and Sxi2a, the targets of which are largely unknown. Here we describe the discovery of a gene, CLP1, that is regulated by Sxi1{alpha} and Sxi2a and is essential for sexual development. In vitro binding studies also show that the CLP1 promoter is bound directly by Sxi1{alpha} and Sxi2a. The deletion of CLP1 leads to a block in sexual development after cell fusion but before filament formation, and cells without CLP1 are unable to grow vegetatively after cell fusion. Our findings lead to a model in which CLP1 is a downstream target of the Sxi proteins that functions to promote growth after mating and establish the filamentous state, a critical step in the production of spores.







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