Basal association of a transcription factor favors early gene expression

Response to extracellular signals via Mitogen-Activated Protein Kinase (MAPK) pathways regulate complex transcriptional programs where hundreds of genes are induced at a desired level with a specific timing. Gene expression regulation is largely encoded in the promoter of the gene, which harbors numerous transcription factor binding sites. In the mating MAPK pathway of Saccharomyces cerevisiae , one major transcription factor, Ste12, controls the chronology of gene expression necessary for the fusion of two haploid cells. Because endogenous promoters encode a wide diversity of Ste12 binding sites (PRE), synthetic promoters were engineered to decipher the rules that dictate mating gene induction. The conformation of PRE dimers that allow efficient gene expression were identified. The strength of binding of Ste12 to the PRE and the distance of the binding sites to the core promoter modulate the level of induction. The speed of activation is ensured by placing a dimer of PRE in a nucleosome depleted region favoring a basal association of Ste12 prior to the stimulus.