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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
,
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-
2 complex
represses white-opaque switching, as well as mating. Based upon the
assumption that the a1-
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.
Published ahead of print on 1 September 2006.
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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