Set1 is a critical transcriptional regulator in response to external signals in Candida albicans.

Precise gene regulation is vital for maintaining cellular homeostasis and enabling environmental adaptation in living organisms. Eukaryotic organisms display intricate transcriptional regulation influenced by chromatin structures and histone modifications. Set1-mediated methylation of histone H3 at lysine 4 (H3K4) is a well-established marker of active transcription in eukaryotes. However, the deletion of Set1 in the dimorphic pathogenic fungus, Candida albicans, led to the activation of signal-responsive genes even in the absence of external signals. The present study aimed to elucidate Set1's role in the transcription of genes that respond to external signals. These inducible genes displayed atypical H3K4 modification patterns. During the initial induction stages, H3K4 methylation was not involved in the rapid and robust expression of these genes; instead, acetylation of the same residue was involved. H3K4 acetylation significantly increased in the absence of H3K4 methylation, allowing genes that did not receive external transcriptional signals to initiate mRNA expression, leading to morphological changes. With continued exposure to induction signals, the heightened H3K4 acetylation decreased while H3K4 methylation increased in these genes. Thus, inducible genes receive positive feedback for stable and sustainable expression. In conclusion, Set1 precisely modulates H3K4 methylation and acetylation levels to regulate the transcription of inducible genes at specific times and levels.