Abstract

Diploid C. albicans cells that are heterozygous for the MTL locus cannot mate, because they repress expression of the master regulatory protein Wor1 critical for activating the mating-competent opaque state. However, cells that lack or are heterozygous for sequences encompassing the shared promoter region of ORFs 19.7061 and 19.7060 can switch to the opaque state even when heterozygous at MTL. Transcriptome analysis of MTL heterozygous strains where one (MA40) or both (MA10) alleles of 5'-UTR of ORF19.7060 were deleted, shows that in spite of the formation of the a1-α2 repressor, the expression of WOR1 occurred, allowing the cells to undergo white-opaque switching. Further investigation revealed that transcription factors such as EFG1, RFG1 and specifically SFL2 were down regulated in both MA10 and MA40 strains. However, these two strains cannot mate properly due to the a1-α2 repression of the mating genes. The ability of the MTL a/α cells to switch to the opaque state appears dependent on the size of the deletions; large deletions in the 5'-UTR of ORF19.7060, even in the heterozygous state, permit switching to classical opaque cells, smaller deletions in this region permit switching to an opaque-like state that exhibits opaque cell morphology but does not express a characteristic opaque-specific epitope on the cell surface, and even smaller deletions are not permissive for white to opaque switching. ORF19.7060, which encodes a protein with sequence similarity to enzymes implicated in non-homologous end joining, is one of the C. albicans genes that have different transcripts in white and opaque cells.