Velvet domain protein VosA represses the zinc cluster transcription factor SclB regulatory network for Aspergillus nidulans asexual development, oxidative stress response and secondary metabolism

Abstract

The NF-κB-like velvet domain protein VosA (viability of spores) binds to more than 1,500 promoter sequences in the filamentous fungus Aspergillus nidulans. VosA inhibits premature induction of the developmental activator gene brlA, which promotes asexual spore formation in response to environmental cues as light. VosA represses a novel genetic network controlled by the sclB gene. SclB function is antagonistic to VosA, because it induces the expression of early activator genes of asexual differentiation as flbC and flbD as well as brlA. The SclB controlled network promotes asexual development and spore viability, but is independent of the fungal light control. SclB interactions with the RcoA transcriptional repressor subunit suggest additional inhibitory functions on transcription. SclB links asexual spore formation to the synthesis of secondary metabolites including emericellamides, austinol as well as dehydroaustinol and activates the oxidative stress response of the fungus. The fungal VosA-SclB regulatory system of transcription includes a VosA control of the sclB promoter, common and opposite VosA and SclB control functions of fungal development and several additional regulatory genes. The relationship between VosA and SclB illustrates the presence of a convoluted surveillance apparatus of transcriptional control, which is required for accurate fungal development and the linkage to the appropriate secondary metabolism.

Integration of Fungus-Specific CandA-C1 into a Trimeric CandA Complex Allowed Splitting of the Gene for the Conserved Receptor Exchange Factor of CullinA E3 Ubiquitin Ligases in Aspergilli

“…The observed mitochondrial dysfunctions might depend on CandA being required for development and secondary metabolism, and on CandA-C1 as essential vegetative growth factor, which might provide additional RNase-associated functions. A connection between asexual development and secondary metabolism was also shown recently for the transcription factor SclB that activates the central regulatory pathway for conidiation (44). All three CandA subunits are obligatory for the multicellular development of sexual ascospores, supporting the idea that regulation of the CRL cycle is required for complex organisms.…”

Velvet activated McrA plays a key role in cellular and metabolic development in Aspergillus nidulans

“…In addition, follow-up studies identified the functions of some target genes and these results provide some clues to elaborate on how these TFs can control spore formation and maturation 29 . For example, the VosA-VelB complex controls the expression of fksA , mtfA , sclB , and vadA , thereby fine-tuning β-glucan synthesis, secondary metabolism, oxidative response, and conidial pigmentation 29 , 31 – 33 , 39 – 41 . This study further expands the VosA/VelB-mediated regulatory networks involving McrA in A. nidulans .…”

“…Genome-wide expression and protein-DNA analyses demonstrated that VosA and VelB directly bind to the promoter regions of many genes such as fksA , tpsA , and brlA , and control their expression 29 , 30 . Further analyses have led us to define additional VosA-VelB target genes such as vadA ( V osA/VelB- A ctivated D evelopmental gene) 31 , mtfA ( M aster TF A) 32 , sclB ( Sc lerotia- l ike B) 33 , and mcrA ( M ulti C luster R egulator A; AN8694) 34 .…”

Genome Sequencing and Analysis of the Hypocrellin-Producing Fungus Shiraia bambusicola S4201

“…The Zn(II)Cys 6 family of transcription factors can regulate various cellular processes in fungi (Thieme et al, 2018). When the zftf gene was overexpressed, expression of the genes in the putative HA cluster was increased, suggesting that the zinc finger transcription factor zftf plays a major role in the regulation of this pathway.…”