Abstract
The filamentous fungus Aspergillus nidulans primarily reproduces by forming asexual spores called conidia and produces the mycotoxin sterigmatocystin (ST), the penultimate precursor of aflatoxins. It has been known that asexual development and ST production are tightly co-regulated by various regulatory inputs. Here, we report that the novel regulator AslA with a C2H2 domain oppositely regulates development and ST biosynthesis. Nullifying aslA resulted in defective conidiation and reduced expression of brlA encoding a key activator of asexual development, which indicates that AslA functions as an upstream activator of brlA expression. aslA deletion additionally caused enhanced ST production and expression of aflR encoding a transcriptional activator for ST biosynthetic genes, suggesting that AslA functions as an upstream negative regulator of aflR. Cellular and molecular studies showed that AslA has a trans-activation domain and is localized in the nuclei of vegetative and developing cells but not in spores, indicating that AslA is likely a transcription factor. Introduction of the aslA homologs from distantly-related aspergilli complemented the defects caused by aslA null mutation in A. nidulans, implying a functional conservancy of AslA. We propose that AslA is a novel regulator that may act at the split control point of the developmental and metabolic pathways.
Highlights
The ascomycete fungus Aspergillus nidulans serves as one of the best model organisms for investing many aspects of cell biology and genetics of filamentous fungi, owing to the extensive available background information on its genetic and biochemical properties
We describe the characterization of the putative C2H2-type zinc finger transcription factor, AslA, in relation to both asexual differentiation and secondary metabolism
While numerous studies over several decades have focused on the processes of development and accompanying metabolic alterations in the model filamentous fungus, A. nidulans, the molecular networks modulating the expression of genes required for asexual differentiation and secondary metabolism remain to be established
Summary
The ascomycete fungus Aspergillus nidulans serves as one of the best model organisms for investing many aspects of cell biology and genetics of filamentous fungi, owing to the extensive available background information on its genetic and biochemical properties. A. nidulans has two major reproductive cycles, asexual and sexual, involving a number of developmental events, including spatiotemporal control of transcription for many genes, specialized cellular differentiation and intercellular communication. The central developmental pathway (CDP) controlling the temporal and spatial expression of conidiation specific genes involves three major regulatory transcription factors (TFs), BrlA, AbaA and WetA5. BrlA functions as a key transcriptional activator of the central regulatory pathway by directing the expression of other genes required for conidiation[5,6,7]. NsdD, a major zinc finger GATA-type activator of sexual reproduction, functions as a key negative regulator of conidiation, potentially exerting a repressive role via downregulating brlA expression[24]. The nuclear protein LaeA was the first-identified transcriptional activator of several secondary metabolite gene clusters in A. nidulans and is well conserved across fungi[29,30]. The secondary metabolite gene clusters subjected to LaeA-dependent regulation contains the genes involved in biosynthesis of sterigmatocystin (ST), such as aflR and stcA-X32–34; and terraquinone (TQ), such as tdiA-E30,35
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