Regulated resource re-allocation is transcriptionally hard wired into the yeast stress response

Many organisms maintain generalized stress responses activated by adverse conditions. Although details vary, a common theme is the redirection of transcriptional and translational capacity away from growth-promoting genes and toward defense genes. Yet the precise roles of these coupled programs are difficult to dissect. Here we investigated Saccharomyces cerevisiae responding to salt as a model stressor. We used molecular, genomic, and single-cell microfluidic methods to examine the interplay between transcription factors Msn2 and Msn4 that induce stress-defense genes and Dot6 and Tod6 that transiently repress growth-promoting genes during stress. Surprisingly, loss of Dot6/Tod6 led to slower acclimation to salt, whereas loss of Msn2/4 produced faster growth during stress. This supports a model where transient repression of growth-promoting genes accelerates the Msn2/4 response, which is essential for acquisition of subsequent peroxide tolerance. Remarkably, we find that Msn2/4 regulate DOT6 transcription, influence Dot6 activation dynamics, and are required for full repression of growth-promoting genes. Thus, Msn2/4 directly regulate the resource re-allocation needed to mount their own response. We discuss broader implications for common stress responses across organisms. Overall design: RNA-seq profiling of Saccharomyces cerevisiae BY4741 strains (wild-type, msn2?msn4?, and dot6?tod6?) before and 10, 20, 30, 40, 50, 60, and 90 minutes after salt stress. Samples were grown in low fluorescent media and harvested at log-phase (proliferative growth). Each strain and timepoint was measured in biological duplicate.