Cross-pathway control gene CPC1/GCN4 coordinates with histone acetyltransferase GCN5 to regulate catalase-3 expression under oxidative stress in Neurospora crassa

Catalase is an important enzyme found in nearly all aerobic organisms and plays an essential role in protecting cells from oxidative damage by catalyzing the degradation of hydrogen peroxide into water and oxygen. In filamentous fungus Neurospora crassa, the expression levels of catalases are rigorously regulated by morphogenetic transition during growth and development in cells. Our study revealed that catalase-3 transcription is positively regulated by histone acetyltransferase GCN5 and the cross-pathway control gene cpc-1, as the cat-3 expression level is significantly decreased in gcn5(KO) and cpc-1 (j-5) mutants. Moreover, gcn5(KO) and cpc-1 (j-5) mutants could not respond to H2O2 treatment due to the inadequate cat-3 transcription, while wild-type strains showed high expression levels of catalase upon H2O2 treatment. The global H3 acetylation and the acetylation of H3 at cat-3 locus dramatically decreased in gcn5(KO) under normal or oxidative stress conditions. Meanwhile, the expression of CAT-3 is reduced in gcn5(E146Q), the catalytically dead mutant, suggesting that the catalytic activity of GCN5 functions in regulation of cat-3 transcription. In addition, GCN5 cannot acetylate histone H-3 efficiently at cat-3 locus in cpc-1 (j-5) mutant strains under normal or oxidative stress conditions. Furthermore, ChIP assays data revealed that the CPC1/GCN4 can directly target the cat-3 promoter region, which may recruit GCN5 to modify the histone acetylation of this region. These results disclosed a distinctive function of CPC1/GCN4 in the regulatory pathway of cat-3 transcription, which is mediated by GCN5-dependent acetylation.