Set1 is a critical transcriptional regulator in response to external signals

Set1-mediated methylation of histone H3 at lysine 4 (H3K4) is a well-established marker of active transcription in eukaryotes. However, absence of Set1 did not significantly alter the overall gene expression; interestingly, some genes exhibited enhanced expression in Candida albicans. The present study aimed to elucidate the role of Set1 in transcription of genes that exhibited increased expression levels in its absence. Ideally, these genes should be repressed and activated in response to specific signals. The hypha-specific genes of C. albicans were expressed in the absence of Set1, even without any external activating signals. These inducible genes displayed atypical H3K4 modification patterns. During the initial induction stages, H3K4 methylation was not involved in the rapid and explosive 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 a positive feedback for stable and sustainable expression. In conclusion, Set1 is a key regulator of transcription in response to external environment changes.