The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals

Sci Rep. 2017 Aug 16;7(1):8308. doi: 10.1038/s41598-017-08239-9.

Abstract

Morphological plasticity such as the yeast-to-hyphae transition is a key virulence factor of the human fungal pathogen Candida albicans. Hyphal formation is controlled by a multilayer regulatory network composed of environmental sensing, signaling, transcriptional modulators as well as chromatin modifications. Here, we demonstrate a novel role for the replication-independent HIR histone chaperone complex in fungal morphogenesis. HIR operates as a crucial modulator of hyphal development, since genetic ablation of the HIR complex subunit Hir1 decreases sensitivity to morphogenetic stimuli. Strikingly, HIR1-deficient cells display altered transcriptional amplitudes upon hyphal initiation, suggesting that Hir1 affects transcription by establishing transcriptional thresholds required for driving morphogenetic cell-fate decisions. Furthermore, ectopic expression of the transcription factor Ume6, which facilitates hyphal maintenance, rescues filamentation defects of hir1Δ/Δ cells, suggesting that Hir1 impacts the early phase of hyphal initiation. Hence, chromatin chaperone-mediated fine-tuning of transcription is crucial for driving morphogenetic conversions in the fungal pathogen C. albicans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / cytology*
  • Candida albicans / physiology*
  • Ectopic Gene Expression
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism*
  • Hyphae / genetics
  • Hyphae / metabolism*
  • Models, Biological
  • Phenotype
  • Signal Transduction*
  • Transcription Factors / metabolism

Substances

  • Fungal Proteins
  • Histone Chaperones
  • Transcription Factors