Genome-wide expression profiling of Candida albicans transcription factor Rme1p

Rme1, a conserved transcription factor among members of the ascomycete lineage, regulates meiosis and pseudohyphal growth in baker’s yeast. The genome of the meiosis-defective fungal pathogen Candida albicans encodes a Rme1 homolog, which we previously mapped within a transcriptional circuitry that controls hyphal growth. To delineate a possible role of Rme1 in C. albicans morphogenesis, we combined genome-wide expression and location analyses of Rme1. Strikingly, Rme1 bound upstream and activated the expression of markers of chlamydosporulation, a process leading to formation of large, spherical, thick-walled cells during nutrient starvation. RME1 deletion abolished chlamydosporulation in three chlamydospore-forming Candida species, whereas its overexpression bypassed the requirement for chlamydosporulation cues and regulators, indicating that Rme1 is central to chlamydospore development. Moreover, RME1 expression levels correlated with chlamydosporulation efficiency among clinical isolates, further highlighting Rme1 importance in this process. Interestingly, RME1 displayed a biphasic pattern of expression, with a first phase independent of Rme1 function and dependent on chlamydospore-inducing cues, and a second phase depending upon Rme1 function and independent of chlamydospore-inducing cues. We suggest that Rme1 function spans from the regulation of meiosis in sexual yeasts to the control of an epigenetic switch necessary for asexual spore formation in meiosis-defective Candida species. Two-condition experiments: 1) Samples 1-6: untreated (-Dox, Cy3-labeled) and Dox-treated (+Dox, Cy5-labeled, 40 µg/mL) during 2h and 4h in Yeast Peptone Dextrose medium, 30C, 3 biological replicates for each time-point; 2) Samples 7-9: Comparison of a Candida albicans wild-type clinical isolate (CEC2018, Cy3-labeled) to an rme1-/- mutant derivative (Cy5-labeled) both grown overnight at 30ºC in YPD medium, then diluted to an OD600 nm of 0.2 in 10 mL of PCB (10% potato/carrot extract and 1.5% dehydrated fresh bile) liquid medium and cultured at 25ºC in the dark and under microaerophilic conditions during 24h.