The Hos2 Histone Deacetylase Controls Ustilago maydis Virulence through Direct Regulation of Mating-Type Genes

Abstract

Morphological changes are critical for host colonisation in plant pathogenic fungi. These changes occur at specific stages of their pathogenic cycle in response to environmental signals and are mediated by transcription factors, which act as master regulators. Histone deacetylases (HDACs) play crucial roles in regulating gene expression, for example by locally modulating the accessibility of chromatin to transcriptional regulators. It has been reported that HDACs play important roles in the virulence of plant fungi. However, the specific environment-sensing pathways that control fungal virulence via HDACs remain poorly characterised. Here we address this question using the maize pathogen Ustilago maydis. We find that the HDAC Hos2 is required for the dimorphic switch and pathogenic development in U. maydis. The deletion of hos2 abolishes the cAMP-dependent expression of mating type genes. Moreover, ChIP experiments detect Hos2 binding to the gene bodies of mating-type genes, which increases in proportion to their expression level following cAMP addition. These observations suggest that Hos2 acts as a downstream component of the cAMP-PKA pathway to control the expression of mating-type genes. Interestingly, we found that Clr3, another HDAC present in U. maydis, also contributes to the cAMP-dependent regulation of mating-type gene expression, demonstrating that Hos2 is not the only HDAC involved in this control system. Overall, our results provide new insights into the role of HDACs in fungal phytopathogenesis.

Pleiotropic effects of the histone deacetylase Hos2 linked to H4-K16 deacetylation, H3-K56 acetylation, and H2A-S129 phosphorylation in Beauveria bassiana

“…This highlights that Hos2 enables to catalyse the H4‐K16 deacetylation required for gene activity in yeasts and some filamentous fungi but is different from the report on the sole H3‐K18 site hyperacetylated in the absence of hos2 in M. oryzae (Ding et al, ). The high sensitivity of our Δ hos2 mutant to trichostatin A is consistent with the U. maydis Δ hos2 response to the same HDAC inhibitor (Elías‐Villalobos et al, ). Intriguingly, the absence of hos2 resulted in unexpected attenuation in H3‐K56 acetylation and drastic repression of the HAT gene Rtt109 responsible for the site‐specific acetylation and DNA damage repair (Chen et al, ; Han et al, ), suggesting an involvement of Hos2 in acetylating H3‐K56 in B. bassiana .…”

“…The hyperacetylation of histone H4‐K16 seen in the Δ hos2 mutant confirms the conserved role for Hos2 in deacetylating the specific histone site in B. bassiana as previously seen in yeasts (Wang et al, ; Wirén et al, ) and U. maydis (Elías‐Villalobos et al, ). This highlights that Hos2 enables to catalyse the H4‐K16 deacetylation required for gene activity in yeasts and some filamentous fungi but is different from the report on the sole H3‐K18 site hyperacetylated in the absence of hos2 in M. oryzae (Ding et al, ).…”

“…These studies unveil vital functions of Hos2 orthologs in filamentous fungal phytopathogens. Interestingly, the Hos2‐deacetylated histone site disclosed in the previous reports is H3‐K18 in M. oryzae (Ding et al, ) but H4‐K16 in U. maydis (Elías‐Villalobos et al, ). The completely different histone sites deacetylated by Hos2 in the two phytopathogenic fungi suggest that Hos2 may mediate different sets of target genes associated with cellular functions in different fungi.…”

“…Hos2 orthologs also exist in filamentous fungi (Brosch, Loidl, & Graessle, ), such as HosA in Aspergillus nidulans (Graessle et al, ) or HDC1 required for extracellular depolymerase expression and virulence in Cochliobolus carbonum (Baidyaroy et al, ). Hos2 has been shown to act as a key component of the Tig1 complex essential for infectious growth and conidiogenesis in Magnaprothe oryzae (Ding et al, ), mediate sexual/asexual development and pathogenesis in Fusarium graminearum (Li et al, ), and act as a downstream component of the cAMP‐PKA pathway and a transcriptional regulator of the mating‐type genes required for dimorphic switch and pathogenesis in Ustilago maydis (Elías‐Villalobos, Fernández‐Álvarez, Moreno‐Sánchez, Helmlinger, & Ibeas, ). These studies unveil vital functions of Hos2 orthologs in filamentous fungal phytopathogens.…”

A Class 1 Histone Deacetylase with Potential as an Antifungal Target

“…In contrast, fungi possess only four to six members of the classical HDAC family (20, 21). In Aspergillus nidulans and its pathogenic relatives, two class 1 enzymes, RpdA and HosA (22, 23), and two class 2 HDACs, HdaA and HosB, were identified and characterized (24) (see Fig.…”