Chromatin regulatory genes differentially interact in networks to facilitate distinct GAL1 activity and noise profiles

Curr Genet. 2021 Apr;67(2):267-281. doi: 10.1007/s00294-020-01124-5. Epub 2020 Nov 7.


Controlling chromatin state constitutes a major regulatory step in gene expression regulation across eukaryotes. While global cellular features or processes are naturally impacted by chromatin state alterations, little is known about how chromatin regulatory genes interact in networks to dictate downstream phenotypes. Using the activity of the canonical galactose network in yeast as a model, here, we measured the impact of the disruption of key chromatin regulatory genes on downstream gene expression, genetic noise and fitness. Using Trichostatin A and nicotinamide, we characterized how drug-based modulation of global histone deacetylase activity affected these phenotypes. Performing epistasis analysis, we discovered phenotype-specific genetic interaction networks of chromatin regulators. Our work provides comprehensive insights into how the galactose network activity is affected by protein interaction networks formed by chromatin regulators.

Keywords: Chromatin regulation; Chromatin state; GAL network; GAL1; Gene expression; Nicotinamide; Noise; TSA; Yeast.

MeSH terms

  • Chromatin / drug effects
  • Chromatin / genetics*
  • Epistasis, Genetic*
  • Galactokinase / genetics*
  • Gene Expression Regulation, Fungal / drug effects
  • Gene Regulatory Networks / genetics
  • Genes, Regulator / genetics
  • Histone Deacetylases / genetics*
  • Hydroxamic Acids / pharmacology
  • Niacinamide / pharmacology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*


  • Chromatin
  • Hydroxamic Acids
  • Saccharomyces cerevisiae Proteins
  • Niacinamide
  • trichostatin A
  • GAL1 protein, S cerevisiae
  • Galactokinase
  • Histone Deacetylases