Different mechanisms confer gradual control and memory at nutrient and stress 1 regulated genes in yeast 2 3 Running title : Dose sensitive gene regulation in yeast 4

23 Cells respond to environmental stimuli by fine tuned regulation of gene expression. 24 Here we investigate the dose dependent modulation of gene expression at high temporal 25 resolution upon nutrient and stress signals in yeast. The GAL1 activity in cell 26 populations is modulated in a well defined range of galactose concentrations, correlating 27 with a dynamic change of histone remodeling and RNAPII association. This behavior is 28 the result of a heterogeneous induction delay by decreasing inducer concentrations 29 across the population. Chromatin remodeling appears to be the basis for the dynamic 30 GAL1 expression because mutants with impaired histone dynamics show severely 31 truncated dose response profiles. In contrast, the GRE2 promoter operates like a rapid 32 off/on switch in response to increasing osmotic stress with almost constant expression 33 rates and exclusively temporal regulation of histone remodeling and RNAPII 34 occupancy. The Gal3 inducer and the Hog1 MAP kinase seem to determine the different 35 dose response strategies at the two promoters. Accordingly, GAL1 becomes highly 36 sensitive and dose independent if previously stimulated because of residual Gal3 levels, 37 whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress 38 resistance. Our analysis reveals important differences in the way dynamic signals create 39 dose sensitive gene expression outputs. 40