The HosA Histone Deacetylase Regulates Aflatoxin Biosynthesis Through Direct Regulation of Aflatoxin Cluster Genes

Mol Plant Microbe Interact. 2019 Sep;32(9):1210-1228. doi: 10.1094/MPMI-01-19-0033-R. Epub 2019 Jul 31.


Histone deacetylases (HDACs) always function as corepressors and sometimes as coactivators in the regulation of fungal development and secondary metabolite production. However, the mechanism through which HDACs play positive roles in secondary metabolite production is still unknown. Here, classical HDAC enzymes were identified and analyzed in Aspergillus flavus, a fungus that produces one of the most carcinogenic secondary metabolites, aflatoxin B1 (AFB1). Characterization of the HDACs revealed that a class I family HDAC, HosA, played crucial roles in growth, reproduction, the oxidative stress response, AFB1 biosynthesis, and pathogenicity. To a lesser extent, a class II family HDAC, HdaA, was also involved in sclerotia formation and AFB1 biosynthesis. An in vitro analysis of HosA revealed that its HDAC activity was considerably diminished at nanomolar concentrations of trichostatin A. Notably, chromatin immunoprecipitation experiments indicated that HosA bound directly to AFB1 biosynthesis cluster genes to regulate their expression. Finally, we found that a transcriptional regulator, SinA, interacts with HosA to regulate fungal development and AFB1 biosynthesis. Overall, our results reveal a novel mechanism by which classical HDACs mediate the induction of secondary metabolite genes in fungi.

Keywords: fungal development; fungal effectors.

MeSH terms

  • Aflatoxins* / biosynthesis
  • Aflatoxins* / genetics
  • Aspergillus flavus* / enzymology
  • Aspergillus flavus* / genetics
  • Aspergillus flavus* / pathogenicity
  • Gene Expression Regulation, Fungal* / genetics
  • Histone Deacetylases* / genetics
  • Histone Deacetylases* / metabolism
  • Protein Binding
  • Virulence / genetics


  • Aflatoxins
  • Histone Deacetylases