Genetic and Molecular Dissection of the Integration of Galactose and Glucose Signaling in Saccharomyces Cerevisiae Strains

Abstract

Cells need to sense the environment in order to survive, in particular they need to detect nutrients which will provide different building blocks and energy for the cell. This task is complicated by the fact that there can be multiple sources for the same type of nutrient available for the cell. A classical example of how cells sense multiple signals is given by carbon catabolite repression in the budding yeast S. cerevisiae. In this model the preferred carbon source glucose represses the genes used to metabolize an alternative source such as galactose. This means that the preferred carbohydrate glucose is thought to inhibit the induction of galactose genes when above a threshold concentration. Instead, we show that galactose metabolic genes (GAL) induction depends on the ratio of galactose and glucose. Surprisingly, we find that a critical portion of information processing occurs upstream of the canonical components of the GAL pathway. We then explore how cells choose between different responses to the environment. Specifically, we set out to characterize the variability in the response to combinations of galactose and glucose between several natural yeast isolates. To elucidate the genetic basis of this phenotypic variation we use QTL mapping on these strains. Our study reveals that a signal transducer GAL3 plays a central role in establishing variation in GAL gene induction.Lastly, we focus on the control of transcription in the cell. Many promoters in the cell produce both a coding transcript and a divergent transcript. To identify mutants that affect transcriptional directionality we use a bidirectionalfluorescent protein reporter in the yeast nonessential gene deletion collection. We determine that chromatin assembly can regulate divergent transcription. Moreover, mutations in the chromatin assembly factor CAF-I can lead to genome wide derepression of nascent divergent transcription.