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Eukaryotic Cell, October 2006, p. 1674-1687, Vol. 5, No. 10
1535-9778/06/$08.00+0     doi:10.1128/EC.00252-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

TOS9 Regulates White-Opaque Switching in Candida albicans{triangledown} ,{dagger}

Thyagarajan Srikantha,1 Anthony R. Borneman,2 Karla J. Daniels,1 Claude Pujol,1 Wei Wu,1 Michael R. Seringhaus,3 Mark Gerstein,3 Song Yi,1 Michael Snyder,2 and David R. Soll1*

Department of Biological Sciences, The University of Iowa, Iowa City, Iowa 52242,1 Department of Molecular, Cellular, and Developmental Biology,2 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 065113

Received 7 August 2006/ Accepted 18 August 2006

In Candida albicans, the a1-{alpha}2 complex represses white-opaque switching, as well as mating. Based upon the assumption that the a1-{alpha}2 corepressor complex binds to the gene that regulates white-opaque switching, a chromatinimmunoprecipitation-microarray analysis strategy was used to identify 52 genes that bound to the complex. One of these genes, TOS9, exhibited an expression pattern consistent with a "master switch gene." TOS9 was only expressed in opaque cells, and its gene product, Tos9p, localized to the nucleus. Deletion of the gene blocked cells in the white phase, misexpression in the white phase caused stable mass conversion of cells to the opaque state, and misexpression blocked temperature-induced mass conversion from the opaque state to the white state. A model was developed for the regulation of spontaneous switching between the opaque state and the white state that includes stochastic changes of Tos9p levels above and below a threshold that induce changes in the chromatin state of an as-yet-unidentified switching locus. TOS9 has also been referred to as EAP2 and WOR1.

* Corresponding author. Mailing address: Department of Biological Sciences, 302 BBE, The University of Iowa, Iowa City, IA 52242. Phone: (319) 335-1117. Fax: (319) 335-2772. E-mail: david-soll{at}uiowa.edu.

{triangledown} Published ahead of print on 1 September 2006.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, October 2006, p. 1674-1687, Vol. 5, No. 10
1535-9778/06/$08.00+0     doi:10.1128/EC.00252-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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