title: Regulation of white and opaque cell-type formation in Candida albicans by Rtt109 and Hst3.
abstract: How different cell types with the same genotype are formed and heritability maintained is a fundamental question in biology. We utilized white-opaque switching in Candida albicans as a system to study mechanisms of cell-type formation and maintenance. Each cell type has tractable characters, which are maintained over many cell divisions. Cell-type specification is under the control of interlocking transcriptional feedback loops, with Wor1 being the master regulator of the opaque cell type. Here we show that deletion of RTT109, encoding the acetyltransferase for histone H3K56, impairs stochastic and environmentally stimulated white-opaque switching. Ectopic expression of WOR1 mostly bypasses the requirement for RTT109, but opaque cells lacking RTT109 cannot be maintained. We have also discovered that nicotinamide induces opaque cell formation, and this activity of nicotinamide requires RTT109. Reducing the copy number of HST3, which encodes the H3K56 deacetylase, also leads to increased opaque formation. We further show that the Hst3 level is downregulated in the presence of genotoxins and ectopic expression of HST3 blocks genotoxin induced switching. This finding links genotoxin induced switching to Hst3 regulation. Together, these findings suggest RTT109 and HST3 genes play an important role in the regulation of white-opaque switching in C. albicans.
authors.affiliation: Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Stevenson
authors.forename: Haoping
authors.initials: H
authors.lastname: Liu
mesh_terms: D002176:Candida albicans / Q000166:cytology* / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D009153:Mutagens; D014157:Transcription Factors; D009536:Niacinamide; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases