Fungus-specific sirtuin HstD coordinates secondary metabolism and development through control of LaeA

Eukaryot Cell. 2013 Aug;12(8):1087-96. doi: 10.1128/EC.00003-13. Epub 2013 May 31.

Abstract

The sirtuins are members of the NAD(+)-dependent histone deacetylase family that contribute to various cellular functions that affect aging, disease, and cancer development in metazoans. However, the physiological roles of the fungus-specific sirtuin family are still poorly understood. Here, we determined a novel function of the fungus-specific sirtuin HstD/Aspergillus oryzae Hst4 (AoHst4), which is a homolog of Hst4 in A. oryzae yeast. The deletion of all histone deacetylases in A. oryzae demonstrated that the fungus-specific sirtuin HstD/AoHst4 is required for the coordination of fungal development and secondary metabolite production. We also show that the expression of the laeA gene, which is the most studied fungus-specific coordinator for the regulation of secondary metabolism and fungal development, was induced in a ΔhstD strain. Genetic interaction analysis of hstD/Aohst4 and laeA clearly indicated that HstD/AoHst4 works upstream of LaeA to coordinate secondary metabolism and fungal development. The hstD/Aohst4 and laeA genes are fungus specific but conserved in the vast family of filamentous fungi. Thus, we conclude that the fungus-specific sirtuin HstD/AoHst4 coordinates fungal development and secondary metabolism via the regulation of LaeA in filamentous fungi.

MeSH terms

  • Aspergillus nidulans / genetics
  • Aspergillus nidulans / metabolism
  • Aspergillus oryzae / genetics
  • Aspergillus oryzae / growth & development*
  • Aspergillus oryzae / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Histone Deacetylases / classification
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Humans
  • Phylogeny
  • Sirtuins / classification
  • Sirtuins / genetics
  • Sirtuins / metabolism*

Substances

  • Fungal Proteins
  • Sirtuins
  • Histone Deacetylases