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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 ,  BZP 2,  GAT 5,  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.

scientific reports

GATA-type transcription factors play a vital role in radiation sensitivity of Cryptococcus neoformans by regulating the gene expression of specific amino acid permeases