SET-1-mediated H3K4me3 modification regulates catalase-3 expression in Neurospora crassa

Clearance and adaptation to reactive oxygen species (ROS) are crucial for cell survival. As in other eukaryotes, the catalases in Neurospora crassa are the main enzymes responsible for ROS clearance, primarily by decomposing hydrogen peroxide (H₂O₂), a major type of ROS. Their expression is tightly regulated by growth and environmental conditions. Histone modifications are frequently linked to the regulation of gene transcription. Histone H3 trimethylation at lysine 4 (H3K4me3) is one of the most studied histone modifications and is associated with transcription initiation. We showed that the abolishment of H3K4me3 in N. crassa led to a low CAT-3 expression level and increased sensitivity to H₂O₂-induced ROS stress. On the other hand, overexpression of the histone methyltransferase SET-1 led to increased expression of CAT-3. Furthermore, ChIP assays revealed that SET-1 mediated H3K4me3 modification at the cat-3 TSS and ORF 5' region, which regulates RNAPII recruitment for cat-3 transcription. Together, these results demonstrate that histone methyltransferase COMPASS (complex of proteins associated with Set1) complex-mediated H3K4me3 plays a key role in activating cat-3 expression in N. crassa.