title: A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis.
abstract: Despite their classical role as transcriptional repressors, several histone deacetylases, including the baker's yeast Set3/Hos2 complex (Set3C), facilitate gene expression. In the dimorphic human pathogen Candida albicans, the homologue of the Set3C inhibits the yeast-to-filament transition, but the precise molecular details of this function have remained elusive. Here, we use a combination of ChIP-Seq and RNA-Seq to show that the Set3C acts as a transcriptional co-factor of metabolic and morphogenesis-related genes in C. albicans. Binding of the Set3C correlates with gene expression during fungal morphogenesis; yet, surprisingly, deletion of SET3 leaves the steady-state expression level of most genes unchanged, both during exponential yeast-phase growth and during the yeast-filament transition. Fine temporal resolution of transcription in cells undergoing this transition revealed that the Set3C modulates transient expression changes of key morphogenesis-related genes. These include a transcription factor cluster comprising of NRG1, EFG1, BRG1, and TEC1, which form a regulatory circuit controlling hyphal differentiation. Set3C appears to restrict the factors by modulating their transcription kinetics, and the hyperfilamentous phenotype of SET3-deficient cells can be reverted by mutating the circuit factors. These results indicate that the chromatin status at coding regions represents a dynamic platform influencing transcription kinetics. Moreover, we suggest that transcription at the coding sequence can be transiently decoupled from potentially conflicting promoter information in dynamic environments.
authors.affiliation: Medical University Vienna, Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories, Vienna, Austria.
authors.forename: Denes
authors.initials: D
authors.lastname: Hnisz
authors.forename: Anaïs F
authors.initials: AF
authors.lastname: Bardet
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Nobile
authors.forename: Andriy
authors.initials: A
authors.lastname: Petryshyn
authors.forename: Walter
authors.initials: W
authors.lastname: Glaser
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schöck
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.forename: Karl
authors.initials: K
authors.lastname: Kuchler
mesh_terms: D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D025301:Hyphae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D007700:Kinetics; D009024:Morphogenesis / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D014157:Transcription Factors; D006655:Histone Deacetylases