Combinatorics of Cis‐Regulatory Element Evolution in Stress Response Modules of Ascomycete Yeasts

This study provides insight into the conservation of cis‐regulatory elements in the osmotic stress response (OSR) of seven ascomycete yeasts. The OSR is orchestrated by the MAP‐kinase HOG1 in Saccaromyces cerevisiae. HOG1 has a human homolog, p38, which regulates the OSR and is known to play a role in angiogenesis. Gene expression profiles under osmotic stress were measured for each ascomycete, only the most induced and most repressed set of genes were evaluated for conservation of cis‐regulatory elements. A programming tool, ModuleDigger, was used to identify cis‐regulatory modules (CRMs), each composed of a set of co‐occurring binding motifs. Species were sorted into two clades: pre‐ and post‐ whole genome duplication (WGD) event. Motifs for the transcription factors RCS1 and SIP4 were present genome‐wide in pre‐WGD duplication and in the fungal pathogens C. albicans and C. glabrata. The post‐whole genome duplication species shared three motif pair combinations (MIG1, MSN2/MSN4; MIG1, ADR1 and ADR1, MSN2/MSN4). These motifs correspond to stress‐responsive elements and carbon‐responsive elements, which suggests interacting biological pathways.