Systematic characterization ofUstilago maydissirtuins shows Sir2 as a modulator of pathogenic gene expression

Abstract

Phytopathogenic fungi must adapt to the different environmental conditions found during infection and avoid the immune response of the plant. For these adaptations, fungi must tightly control gene expression, allowing sequential changes in transcriptional programs. In addition to transcription factors, chromatin modification is used by eukaryotic cells as a different layer of transcriptional control. Specifically, the acetylation of histones is one of the chromatin modifications with a strong impact on gene expression. Hyperacetylated regions usually correlate with high transcription and hypoacetylated areas with low transcription. Thus, histone deacetylases (HDACs) commonly act as repressors of transcription. One member of the family of HDACs is represented by sirtuins, which are deacetylases dependent on NAD+, and, thus, their activity is considered to be related to the physiological stage of the cells. This property makes sirtuins good regulators during environmental changes. However, only a few examples exist, and with differences in the extent of the implication of the role of sirtuins during fungal phytopathogenesis. In this work, we have performed a systematic study of sirtuins in the maize pathogen Ustilago maydis, finding Sir2 to be involved in the dimorphic switch from yeast cell to filament and pathogenic development. Specifically, the deletion of sir2 promotes filamentation, whereas its overexpression highly reduces tumor formation in the plant. Moreover, transcriptomic analysis revealed that Sir2 represses genes that are expressed during biotrophism development. Interestingly, our results suggest that this repressive effect is not through histone deacetylation, indicating a different target of Sir2 in this fungus.

Sir2‐mediated cytoplasmic deacetylation facilitates pathogenic fungi infection in host plants

“…In plant fungi, several Sir2 family deacetylases have been characterized, which distributed in nuclei and functioned as modulators of pathogenic gene expression (Fernandez et al ., 2014; Cai et al ., 2021; Navarrete et al ., 2023). Our previous study showed that the Fol sirtuin FolSir2 predominantly resides in the cytoplasm (Zhang et al ., 2023), which is different from the rest of these proteins.…”

“…B. Li et al ., 2020), the complicated interactions among the multiple substrates may contribute to the unaffected phenotype in mycelial growth of FolSir2 knockout mutants. Similar results can be observed in U. maydis and M. oryzae , in which loss of UmSir2 and MoSir2 function in Δsir2 strains did not affect fungal growth, but attenuated the virulence (Fernandez et al ., 2014; Navarrete et al ., 2023). Moreover, FolSir2 homologues with similar functions are also present in B. cinerea and other phytopathogenic fungi.…”

“…Although poorly studied, filamentous fungi possess Sir2 homologues. In the plant pathogen Ustilago maydis , deletion of the nuclear Sir2 homologue, UmSir2, promotes filamentation, whereas its overexpression reduces tumour formation in the plant (Navarrete et al ., 2023). In Magnaporthe oryzae , MoSir2 was shown to be mainly located in nuclei and required for host reactive oxygen species burst neutralization and knockout of MoSir2 led to decreased biotrophic growth in host rice plants (Fernandez et al ., 2014; G. Li et al ., 2020).…”

Epigenetic regulation of nuclear processes in fungal plant pathogens

“…In these fungi, deletion of genes encoding HAT family members affected fungal virulence as well as lifestyle switches [60][61][62]. In U. maydis, activity of the HDAC member Sir2 is involved in pathogenic development, although it is unclear whether Sir2 is truly active in deacetylation [63]. Recent results in Saccharomyces cerevisiae have raised concerns about the role of histone acetylation in transcriptional regulation, as temporal experiments show that transcriptional activation occurs before histone acetylation, which suggests that even though histone acetylation may be involved in transcriptional regulation during disease development, it may not directly activate transcription [64].…”