TOS9 regulates white-opaque switching in Candida albicans

Eukaryot Cell. 2006 Oct;5(10):1674-87. doi: 10.1128/EC.00252-06. Epub 2006 Sep 1.

Abstract

In Candida albicans, the a1-alpha2 complex represses white-opaque switching, as well as mating. Based upon the assumption that the a1-alpha2 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Candida albicans / cytology
  • Candida albicans / metabolism*
  • Cell Nucleus / metabolism
  • Chromatin Immunoprecipitation
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Genes, Mating Type, Fungal / genetics
  • Genes, Switch / genetics*
  • Genome, Fungal / genetics
  • Genotype
  • Models, Genetic
  • Protein Binding
  • Protein Transport
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Temperature
  • Transcription, Genetic

Substances

  • Fungal Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Recombinant Fusion Proteins