Sirtuin E is a fungal global transcriptional regulator that determines the transition from the primary growth to the stationary phase

J Biol Chem. 2017 Jun 30;292(26):11043-11054. doi: 10.1074/jbc.M116.753772. Epub 2017 May 2.

Abstract

In response to limited nutrients, fungal cells exit the primary growth phase, enter the stationary phase, and cease proliferation. Although fundamental to microbial physiology in many environments, the regulation of this transition is poorly understood but likely involves many transcriptional regulators. These may include the sirtuins, which deacetylate acetyllysine residues of histones and epigenetically regulate global transcription. Therefore, we investigated the role of a nuclear sirtuin, sirtuin E (SirE), from the ascomycete fungus Aspergillus nidulans An A. nidulans strain with a disrupted sirE gene (SirEΔ) accumulated more acetylated histone H3 during the stationary growth phase when sirE was expressed at increased levels in the wild type. SirEΔ exhibited decreased mycelial autolysis, conidiophore development, sterigmatocystin biosynthesis, and production of extracellular hydrolases. Moreover, the transcription of the genes involved in these processes was also decreased, indicating that SirE is a histone deacetylase that up-regulates these activities in the stationary growth phase. Transcriptome analyses indicated that SirE repressed primary carbon and nitrogen metabolism and cell-wall synthesis. Chromatin immunoprecipitation demonstrated that SirE deacetylates acetylated Lys-9 residues in histone H3 at the gene promoters of α-1,3-glucan synthase (agsB), glycolytic phosphofructokinase (pfkA), and glyceraldehyde 3-phosphate (gpdA), indicating that SirE represses the expression of these primary metabolic genes. In summary, these results indicate that SirE facilitates the metabolic transition from the primary growth phase to the stationary phase. Because the observed gene expression profiles in stationary phase matched those resulting from carbon starvation, SirE appears to control this metabolic transition via a mechanism associated with the starvation response.

Keywords: Aspergillus; autolysis; glucose metabolism; secondary metabolism; sirtuin; sporulation.

MeSH terms

  • Aspergillus nidulans / genetics
  • Aspergillus nidulans / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal / physiology*
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptome / physiology*

Substances

  • Fungal Proteins
  • Transcription Factors
  • Sirtuins