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.

控制染色质状态是真核生物基因表达调控中的一个主要调控步骤。虽然全球细胞特征或过程自然会受到染色质状态改变的影响，但对于染色质调控基因如何在网络中相互作用以决定下游表型，我们知之甚少。在这里，我们以酵母中典型半乳糖网络的活性为模型，测量了关键染色质调控基因的破坏对下游基因表达、遗传噪声和适应度的影响。使用曲古抑菌素 A 和烟酰胺，我们描述了基于药物的全局组蛋白脱乙酰酶活性调节如何影响这些表型。通过上位性分析，我们发现了染色质调节剂的表型特异性遗传相互作用网络。