HDA-2-Containing Complex Is Required for Activation of Catalase-3 Expression in Neurospora crassa

Abstract

ABSTRACT It is essential for aerobic organisms to maintain the homeostasis of intracellular reactive oxygen species (ROS) for survival and adaptation to the environment. In line with other eukaryotes, the catalase of Neurospora crassa is an important enzyme for clearing ROS, and its expression is tightly regulated by the growth phase and various oxidative stresses. Our study reveals that, in N. crassa, histone deacetylase 2 (HDA-2) and its catalytic activity positively regulate the expression of the catalase-3 (cat-3) gene. HDA-2, SIF-2, and SNT-1 may form a subcomplex with such a regulation role. As expected, deletion of HDA-2 or SIF-2 subunit increased acetylation levels of histone H4, indicating that loss of HDA-2 complex fails to deacetylate H4 at the cat-3 locus. Furthermore, loss of HDA-2 or its catalytic activity led to dramatic decreases of TFIIB and RNA polymerase II (RNAP II) recruitment at the cat-3 locus and also resulted in high deposition of H2A.Z at the promoter and transcription start site (TSS) regions of the cat-3 gene. Collectively, this study strongly demonstrates that the HDA-2-containing complex activates the transcription of the cat-3 gene by facilitating preinitiation complex (PIC) assembly and antagonizing the inhibition of H2A.Z at the cat-3 locus through H4 acetylation. IMPORTANCE Clearance of reactive oxygen species (ROS) is critical to the survival of aerobic organisms. In the model filamentous fungus Neurospora crassa, catalase-3 (cat-3) expression is activated in response to H2O2-induced ROS stress. We found that histone deacetylase 2 (HDA-2) positively regulates cat-3 transcription in N. crassa; this is widely divergent from the classical repressive role of most histone deacetylases. Like HDA-2, the SIF-2 or SNT-1 subunit of HDA-2-containing complex plays a positive role in cat-3 transcription. Furthermore, we also found that HDA-2-containing complex provides an appropriate chromatin environment to facilitate PIC assembly and to antagonize the inhibition role of H2A.Z at the cat-3 locus through H4 acetylation. Taken together, our results establish a mechanism for how the HDA-2-containing complex regulates transcription of the cat-3 gene in N. crassa.

Keywords

• HDA-2
• Histone H4 acetylation
• Catalase-3
• Neurospora crassa