A push-pull system of repressors matches levels of glucose transporters to extracellular glucose in budding yeast

Cells can match expression of a series of genes to a signal, so that each gene expresses in a particular range of the signal. An example is glucose transport in budding yeast where cells express different hexose-transporter (\g{HXT}) genes in different ranges of concentrations of extracellular glucose. Here we determine mechanistically how this matching to glucose occurs using time-lapse microscopy, microfluidics, dynamic glucose inputs, and mathematical modelling. We show that the glucose-sensing network works to generate a push-pull system of two pairs of repressors: as glucose rises, cells `pull' repression by two regulators, Mth1 and Std1, decreasing their activity while `pushing' repression by two others, Mig1 and Mig2; in falling glucose, cells reverse the push-pull. The combined activity of these repressors is an intracellular readout of extracellular glucose. Cells express those transporters with an affinity matching the current glucose concentration because the HXT promoters couple to the repressors in three principal ways, each specific to either low, medium, or high-affinity transporters. Through this regulation, budding yeast likely excels at importing glucose rapidly. Matching gene expression to a pattern of input is fundamental, and we believe that push-pull repression is likely widespread.