| The velvet regulators are the key players coordinating fungal growth, differentiation and secondary metabolism in response to various internal and external cues. This dissertation describes the roles of the four velvet regulators, VeA, VelB, VelC and VosA in the model fungus Aspergillus nidulans and the opportunistic human pathogen Aspergillus fumigatus . In A. nidulans, VelB acts as a positive regulator of asexual development and regulates spore maturation, focal trehalose biogenesis and germination. VelC positively regulates sexual development and indirectly represses conidiophore production. The velvet proteins interact with other velvet regulators or non-velvet proteins resulting in the formation cell-type and/or time specific complexes that play differential roles in regulating development, sporogenesis and toxigenesis. Among the velvet complexes, the VelB-VosA hetero-complex acts as a functional unit conferring the completion of sporogenesis (focal trehalose biogenesis and spore wall completion), long-term viability of the spore, and the attenuation of conidial germination in Aspergillus nidulans. In A. fumigatus, the velvet regulators play similar yet somewhat distinct roles in asexual development and sporulation. The deletion of AfuveA, AfuvelB, and AfuvosA causes hyper-active asexual development (conidiation) and precocious and elevated accumulation of AfubrlA. During spore maturation, AfuVelB and AfuVosA play an interdependent role in trehalose biosynthesis, spore dormancy and conidial germination. The deletion of veA can be fully complemented by A. nidulans VeA, which can physically interact with AfuVelB and AfuLaeA in vivo. Finally, crystal structure analysis of the VosA velvet domain revealed an unexpected structural similarity with the Rel homology domain (RHD) of the mammalian transcription factor NF-κB. The velvet domain of VosA contains DNA-binding ability and specifically recognizes the consensus DNA sequence in promoters of developmental genes. Overall, the velvet family proteins are fungal specific transcription factors with DNA-binding ability and are key players coordinating fungal growth, differentiation, pathogenicity, and secondary metabolism in filamentous and dimorphic fungi. |
