The Swi-Snf chromatin remodeling complex mediates gene activation through metabolic control [ChIP-seq II]

In eukaryotes, ATP-dependent chromatin remodelers regulate gene expression in response to nutritional and metabolic stimuli. The Swi-Snf complex is one such remodeler that has been implicated in disease, where loss of Swi-Snf function leads to dysregulated gene transcription. However, altered transcription of metabolic genes may have consequences for entire pathways that remain poorly understood. In this study, we use genetic and molecular approaches to uncover a role for Swi-Snf as a critical regulator of metabolism. We find that ?snf mutants are cysteine-deficient, despite growth in nutrient-rich media. This cysteine deficiency causes widespread perturbations in sulfur metabolic gene transcription. This includes global alteration and redistribution of the transcription factor Met4 which senses cysteine deficiency and also has roles in heavy metal stress response and cell cycle progression. Additionally, we show that in its role as a metabolic regulator, Swi-Snf is a critical determinant of survival following oxidative stress. Our findings show how a chromatin remodeler can have a significant impact on a whole metabolic pathway by directly regulating an important gene subset and demonstrate an emerging role for chromatin remodeling complexes as key determinants of metabolic control. Overall design: Met4 was conditionally depleted in wt and snf2 mutant strains by the anchor away method and RNA polymerase II (Rpb1 subunit) occupancy was monitored by ChIP