The Histone Deacetylase Genes HDA1 and RPD3 Play Distinct Roles in Regulation of High-Frequency Phenotypic Switching in Candida albicans

doi:10.1128/JB.183.15.4614-4625.2001

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Journal of Bacteriology, August 2001, p. 4614-4625, Vol. 183, No. 15
0021-9193/01/$04.00+0 DOI: 10.1128/JB.183.15.4614-4625.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Histone Deacetylase Genes HDA1 and RPD3 Play Distinct Roles in Regulation of High-Frequency Phenotypic Switching in Candida albicans

T. Srikantha,¹ L. Tsai,¹ K. Daniels,¹ A. J. S. Klar,² and D. R. Soll¹^,^*

Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242,¹ and Developmental Genetics Section, Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702²

Received 26 February 2001/Accepted 16 May 2001

Five histone deacetylase genes (HDA1, RPD3, HOS1, HOS2, and HOS3) have been cloned from Candida albicans and characterized.Sequence analysis and comparison with 17 additional deacetylasesresulted in a phylogenetic tree composed of three major groups.Transcription of the deacetylases HDA1 and RPD3 is down-regulatedin the opaque phase of the white-opaque transition in strain WO-1.HOS3 is selectively transcribed as a 2.5-kb transcript in thewhite phase and as a less-abundant 2.3-kb transcript in the opaquephase. HDA1 and RPD3 were independently deleted in strain WO-1,and both switching between the white and opaque phases and thedownstream regulation of phase-specific genes were analyzed. Deletionof HDA1 resulted in an increase in the frequency of switchingfrom the white phase to the opaque phase, but had no effect onthe frequency of switching from the opaque phase to the whitephase. Deletion of RPD3 resulted in an increase in the frequencyof switching in both directions. Deletion of HDA1 resulted inreduced white-phase-specific expression of the EFG1 3.2-kb transcript,but had no significant effect on white-phase-specific expressionof WH11 or opaque-phase-specific expression of OP4, SAP1, andSAP3. Deletion of RPD3 resulted in reduced opaque-phase-specificexpression of OP4, SAP1, and SAP3 and a slight reduction of white-phase-specificexpression of WH11 and 3.2-kb EFG1. Deletion of neither HDA1 norRPD3 affected the high level of white-phase expression and thelow level of opaque-phase expression of the MADS box protein geneMCM1, which has been implicated in the regulation of opaque-phase-specificgene expression. In addition, there was no effect on the phase-regulatedlevels of expression of the other deacetylase genes. These resultsdemonstrate that the two deacetylase genes HDA1 and RPD3 playdistinct roles in the suppression of switching, that the two playdistinct and selective roles in the regulation of phase-specificgenes, and that the deacetylases are in turn regulated byswitching.

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

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