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Functional dissection of the regulatory mechanism of the atypical AP-1-like transcription factor, Yap1, in Cryptococcus neoformans

ABSTRACT: AP-1 like transcription factors play evolutionarily conserved roles in oxidative stress responses as redox sensors in eukaryotes. In this study, we aim to elucidate the regulatory mechanism of an atypical yeast AP-1 like protein, Yap1, in the stress response and virulence of Cryptococcus neoformans. YAP1 expression was induced not only by oxidative stresses, such as H2O2 and diamide, but also by other environmental stresses, such as osmotic and membrane destabilizing stresses. Supporting these data, Yap1 was involved in osmotic and membrane stress responses as well as oxidative stress responses. Pleiotropic roles of Yap1 in diverse biological processes were supported by transcriptome analysis data showing that more than 162 genes are differentially regulated by Yap1. This analysis also provided a clue that Yap1 is involved in carbohydrate metabolism and indeed we found that Yap1 promotes cellular resistance to toxic cellular metabolites produced during glycolysis, such as methylglyoxal. Finally, we demonstrated that Yap1 played a minor role in survival of C. neoformans within hosts.

ORGANISM(S): Cryptococcus neoformans var. grubii H99

PROVIDER: GSE136832 | GEO | 2019/11/07

REPOSITORIES: GEO

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Project description:Genome wide transcriptional changes induced by various types of oxidative stresses as well as salt stress were studied in a DatfA mutant and the appropriate control A. nidulans strains. Although a significant number of stereotypically regulated genes was identified (Core Oxidative Stress Response or COSR genes) when the global transcriptional effects of five different oxidative stress conditions were compared the number of co-regulated genes decreased to 13 when NaCl stress was included into the analyses. The appearance of only a few co-regulated genes and the great number of genes regulated merely by one certain type of stress do not support the existence of a S. cerevisiae-type Environmental Stress Response in A. nidulans. Deletion of atfA, a true functional ortholog of fission yeastâs âall-purposeâ stress response transcription factor, increased the oxidative stress sensitivity of A. nidulans and affected the transcription of several genes under both unstressed and stressed conditions. The number of genes under AtfA control was quite stress-type dependent; e.g. deletion of atfA altered the transcription of a wide spectrum of genes under menadione sodium bisulfite stress but had only a minor effect on the transcriptome profiles when A. nidulans cultures were exposed to H2O2, tBOOH, NaCl and, especially, to diamide stress. These observations suggest that the function of AtfA in the regulation of various stress responses is much smaller than we thought before or other transcription factors can take over a number of AtfAâs functions when the atfA gene is deleted. It is noteworthy that both oxidative and salt stress induced the transcription of some secondary metabolite gene clusters and the deletion of atfA enhanced the stress responsiveness of further clusters. Surprisingly, certain clusters were down-regulated by the stress conditions tested and the majority of them were not stress-responsive at all. Therefore, stress dependent regulation seems to be a frequent but far not a general feature of the regulation of secondary metabolism in A. nidulans. 14 samples, 7 with the control strain and 7 with an DatfA strain (each series contains samples from untreated as well as menadione, low concentration hidrogen-peroxide, high concentration hidrogen-peroxide, tert-butylhydroperoxide, diamide and NaCl treated cultures)

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Functional dissection of the regulatory mechanism of the atypical AP-1-like transcription factor, Yap1, in Cryptococcus neoformans

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