A network of transcription factors in complex with a regulating cell cycle cyclin orchestrates fungal oxidative stress responses

• Published in: BMC biology 2024-04, Vol.22 (1), p.81-81, Article 81
• Main Authors: Kan, Yanze, He, Zhangjiang, Keyhani, Nemat O, Li, Ning, Huang, Shuaishuai, Zhao, Xin, Liu, Pengfei, Zeng, Fanqin, Li, Min, Luo, Zhibing, Zhang, Yongjun
• Format: Article
• Language: English
• Subjects: Analysis; Antioxidants; Binding; Cell Cycle; Cell death; Cellular stress response; Chromatin; Chromatin immunoprecipitation; Cloning; Complex formation; Cyclins; Detoxification; DNA binding proteins; Free radicals; Fungal pathogen; Fungi; Gene expression; Gene regulation; Gene sequencing; Genes; Genomes; Genotype & phenotype; Health aspects; Homeostasis; Hydrogen Peroxide; Hypoxia; Immunoprecipitation; Infections; Insects; Kinases; MAP kinase; Membrane proteins; Menadione; Metabolites; Oxidative Stress; Oxidative stress response; Pathogens; Phosphorylation; Promoters; Protein complex; Proteins; Regulation; RNA; Sequence analysis; Tolerances; Tolerances (dimensional); Transcription; Transcription factor; Transcription factors; Transcription Factors - genetics; Virulence; Virulence (Microbiology); Yeast
• ISSN: 1741-7007; 1741-7007
• DOI: 10.1186/s12915-024-01884-3

Response to oxidative stress is universal in almost all organisms and the mitochondrial membrane protein, BbOhmm, negatively affects oxidative stress responses and virulence in the insect fungal pathogen, Beauveria bassiana. Nothing further, however, is known concerning how BbOhmm and this phenomenon is regulated. Three oxidative stress response regulating Zn Cys transcription factors (BbOsrR1, 2, and 3) were identified and verified via chromatin immunoprecipitation (ChIP)-qPCR analysis as binding to the BbOhmm promoter region, with BbOsrR2 showing the strongest binding. Targeted gene knockout of BbOsrR1 or BbOsrR3 led to decreased BbOhmm expression and consequently increased tolerances to free radical generating compounds (H O and menadione), whereas the ΔBbOsrR2 strain showed increased BbOhmm expression with concomitant decreased tolerances to these compounds. RNA and ChIP sequencing analysis revealed that BbOsrR1 directly regulated a wide range of antioxidation and transcription-associated genes, negatively affecting the expression of the BbClp1 cyclin and BbOsrR2. BbClp1 was shown to localize to the cell nucleus and negatively mediate oxidative stress responses. BbOsrR2 and BbOsrR3 were shown to feed into the Fus3-MAPK pathway in addition to regulating antioxidation and detoxification genes. Binding motifs for the three transcription factors were found to partially overlap in the promoter region of BbOhmm and other target genes. Whereas BbOsrR1 appeared to function independently, co-immunoprecipitation revealed complex formation between BbClp1, BbOsrR2, and BbOsrR3, with BbClp1 partially regulating BbOsrR2 phosphorylation. These findings reveal a regulatory network mediated by BbOsrR1 and the formation of a BbClp1-BbOsrR2-BbOsrR3 complex that orchestrates fungal oxidative stress responses.