Abstract
Cryptococcus neoformans is a basidiomycete fungus that is highly resistant to ionizing radiation and has been identified in highly radioactive environments. Transcription factors (TFs) are master regulators of gene expression by binding to specific DNA sequences within promoters of target genes. A library of 322 signature-tagged gene deletion strains for 155 C. neoformans TF genes has been established. Previous phenome-based functional analysis of the C. neoformans TF mutant library identified key TFs important for various phenotypes, such as growth, differentiation, virulence-factor production, and stress responses. Here, utilizing the established TF mutant library, we identified 5 TFs that are important for radiation sensitivity, including SRE1, BZP2, GAT5, GAT6, and HCM1. Interestingly, BZP2, GAT5 and GAT6 all belong to the GATA-type transcription factors. These factors regulate transcription of nitrogen catabolite repression (NCR) sensitive genes when preferred nitrogen sources are absent or limiting. In addition to radiation, we found that specific GATA factors are important for other stressors such as rapamycin, fluconazole, and hydroxyurea treatment. Using real-time PCR method, we studied the expression of GATA down-stream genes after radiation exposure and identified that AAP4, AAP5 and URO1 were differentially expressed in the GAT5 and GAT6 mutants compared to the wild type cells. In summary, our data suggest that GATA TFs are important for radiation sensitivity in C. neoformans by regulating specific downstream AAP genes.
Highlights
It is well established that ionizing radiation (IR) causes deleterious effects on cell survival by causing damages to cellular macromolecules including nucleic acids, proteins and lipids
We identified Transcription factors (TFs) and their downstream genes that play important roles in radiation resistance in C. neoformans, which is a highly radiation-resistant fungus found in highly radioactive environment
We found that specific GATA TFs play important roles in C. neoformans after radiation exposure
Summary
It is well established that ionizing radiation (IR) causes deleterious effects on cell survival by causing damages to cellular macromolecules including nucleic acids, proteins and lipids. Transcription factors (TFs) are key regulators for gene expression coordination and their study is very important for understanding the molecular mechanisms of development and responses to environmental signals[8]. Jung et al constructed a systematic C. neoformans TF mutant library, which consists of 322 signature-tagged gene-deletion strains for 155 putative TF genes predicted by bioinformatics analysis[11]. Using this library, TFs important for 32 distinct growth conditions have been identified[11]. We exposed the C. neoformans TF mutant library to high dose γ-radiation, and identified several TFs that are important for radiation sensitivity. Our study provides better understanding of the transcriptional circuits in the C. neoformans after radiation exposure
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