Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi

Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Chromatin modifications represent a well-known layer of regulation that controls gene expression in response to environmental signals. However, less is known about the chromatin modifications that are involved in fungal virulence and the specific cues and signalling pathways that target chromatin modifications to specific genes. In a recently published study, our research group identified one such regulatory pathway. We demonstrated that the histone deacetylase (HDAC) Hos2 is involved in yeast-tohyphal transition (dimorphism) and it is associated with the virulence of the maize pathogen Ustilago maydis , the causative agent of smut disease in corn. Hos2 activates mating-type genes by directly binding to their gene bodies. Furthermore, Hos2 acts downstream of the nutrient-sensing cyclic AMP-Protein Kinase A pathway. We also found that another HDAC, Clr3, contributes to this regulation, possibly in cooperation with Hos2. As a whole, our data suggest that there is a direct link between changes in the environment and acetylation of nucleosomes within certain genes. We propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis. Plant pathogenic fungi need to undergo a series of morphological changes in particular phases of their infection cycle. The success of infection depends on the proper timing of these changes. U. maydis starts its pathogenic cycle with a morphological shift from a yeast-like form to a polarized filament on the surface of the maize leaf, a process controlled by factors encoded by the mating-type loci. The a locus encodes for the pheromone-receptor system, which allows the recognition and fusion of sexuallycompatible haploid cells. The fate of the resulting dicaryon is then determined by the b locus, which encodes for transcription factors that form a compatible heterodimer only when co-expressed by cells of the opposite mating type, thus promoting filamentation and virulence. The expression of genes at the a and b loci is controlled by the prf1 transcription factor, which is activated both by the cAMPPKA pathway and the pheromone-responsive Mitogen Activated Protein Kinase (MAPK) cascade at transcriptional and posttranslational level. The regulation of mating genes is therefore critical to ensuring the initiation of the pathogenic program in the smut fungus. Several transcription factors have been shown to regulate these genes by directly or indirectly affecting prf1 expression, yet very little is known about their regulation by chromatin-modifying factors. We addressed this question by analysing the role of histone deacetylation in dimorphic switch and virulence in U. maydis . Histone acetylation and deacetylation represent a gen