The interaction between the histone acetyltransferase complex Hat1-Hat2 and transcription factor AmyR provides a molecular brake to regulate amylase gene expression

Mol Microbiol. 2023 Apr;119(4):471-491. doi: 10.1111/mmi.15036. Epub 2023 Feb 14.

Abstract

The chromatin structure is generally regulated by chromatin remodelers and histone modifiers, which affect DNA replication, repair, and levels of transcription. The first identified histone acetyltransferase was Hat1/KAT1, which belongs to lysine (K) acetyltransferases. The catalytic subunit Hat1 and the regulatory subunit Hat2 make up the core HAT1 complex. In this study, the results of tandem affinity purification and mass spectrometry and bimolecular fluorescence complementation proved that the Penicillium oxalicum PoHat1-Hat2 is the transcriptional cofactor of the sequence-specific transcription factor PoAmyR, a transcription activator essential for the transcription of amylase gene. ChIP-qPCR results demonstrated that the complex PoHat1-Hat2 is recruited by PoAmyR to the promoters of prominent amylase genes Poamy13A and Poamy15A and performs histone H4 lysine12 acetylation. The result of the yeast two-hybrid test indicated that PoHat2 is the subunit that directly interacts with PoAmyR. PoHat1-Hat2 acts as the molecular brake of the PoAmyR-regulating transcription of amylase genes. A putative model for amylase gene regulation by PoAmyR-Hat2-Hat1 was constructed. Our paper is the first report that the Hat1-Hat2 complex acts as a cofactor for sequence-specific TF to regulate gene expression and explains the mechanism of TF AmyR regulating amylase genes expression.

Keywords: amylase; cofactors; fungi; histone acetyltransferases; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Chromatin
  • Fungal Proteins* / metabolism
  • Gene Expression
  • Histone Acetyltransferases* / genetics
  • Histone Acetyltransferases* / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Penicillium* / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Chromatin
  • Histone Acetyltransferases
  • Histones
  • Transcription Factors
  • Fungal Proteins

Supplementary concepts

  • Penicillium oxalicum