Conservation and divergence in the asexual development gene regulatory network across a genus of filamentous fungi
Ontology highlight
ABSTRACT:
ORGANISM(S): Aspergillus fumigatus Aspergillus nidulans
PROVIDER: GSE114167 | GEO | 2018/07/24
REPOSITORIES: GEO
Similar Datasets
Project description:Asexual development is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In the filamentous fungal genus Aspergillus, the production of asexual spores is primarily governed by the BrlA-AbaA-WetA central regulatory cascade. The final step in this cascade, which is controlled by the WetA protein, not only governs cellular development (i.e., the morphological differentiation of spores) but also ensures its coupling with chemical development (i.e., the coordinated production and deposition of diverse secondary metabolites, such as aflatoxins, into spores). While the wetA gene is conserved across the genus Aspergillus, the structure and degree of conservation of the BrlA-AbaA-WetA regulatory cascade and the broader wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type (WT) asexual spores in three representative species spanning the diversity of the genus Aspergillus: the genetic model A. nidulans, the agricultural pest A. flavus, and the human pathogen A. fumigatus. We discovered that WetA regulates asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascade’s first step. Furthermore, ChIP-seq experiments in A. nidulans asexual spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory element, which we term the WetA Response Element (WRE). Interestingly, the WRE is found completely conserved in the non-coding region upstream of the wetA translation start site of many diverse Aspergillus genomes. In contrast, several global transcriptional regulators, most notably those in the velvet complex (veA, velB, and laeA) known to regulate the coupling between asexual development and production of secondary metabolites, show species-specific regulatory patterns. These results suggest that the BrlA-AbaA-WetA cascade’s regulatory role in cellular and chemical development of asexual spores is functionally conserved, but that the WetA-associated GRN has diverged during Aspergillus evolution. This entry is for the ChIP-seq data.
2018-07-24 | GSE114141 | GEO
Project description:Asexual development is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In the filamentous fungal genus Aspergillus, the production of asexual spores is primarily governed by the BrlA-AbaA-WetA central regulatory cascade. The final step in this cascade, which is controlled by the WetA protein, not only governs cellular development (i.e., the morphological differentiation of spores) but also ensures its coupling with chemical development (i.e., the coordinated production and deposition of diverse secondary metabolites, such as aflatoxins, into spores). While the wetA gene is conserved across the genus Aspergillus, the structure and degree of conservation of the BrlA-AbaA-WetA regulatory cascade and the broader wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type (WT) asexual spores in three representative species spanning the diversity of the genus Aspergillus: the genetic model A. nidulans, the agricultural pest A. flavus, and the human pathogen A. fumigatus. We discovered that WetA regulates asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascade’s first step. Furthermore, ChIP-seq experiments in A. nidulans asexual spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory element, which we term the WetA Response Element (WRE). Interestingly, the WRE is found completely conserved in the non-coding region upstream of the wetA translation start site of many diverse Aspergillus genomes. In contrast, several global transcriptional regulators, most notably those in the velvet complex (veA, velB, and laeA) known to regulate the coupling between asexual development and production of secondary metabolites, show species-specific regulatory patterns. These results suggest that the BrlA-AbaA-WetA cascade’s regulatory role in cellular and chemical development of asexual spores is functionally conserved, but that the WetA-associated GRN has diverged during Aspergillus evolution. This entry is for the RNA-seq data.
2018-07-24 | GSE114143 | GEO
Project description:Conservation and divergence in the asexual development gene regulatory network across a genus of filamentous fungi
| PRJNA466232 | ENA
Project description:Conservation and divergence in the asexual development gene regulatory network across a genus of filamentous fungi [ChIP-seq]
| PRJNA465908 | ENA
Project description:Conservation and divergence in the asexual development gene regulatory network across a genus of filamentous fungi [RNA-seq]
| PRJNA466069 | ENA
Project description:Understanding the p53 tumor suppressor pathway remains crucial for the design of anticancer strategies. Studies in human tumors and mouse models help to unravel the molecular mechanisms that underlie the p53 signaling pathway. Yet, the p53 gene regulatory network (GRN) is not the same in mice and humans. The comparison of the regulatory networks of p53 in mice and humans reveals that gene up- and down-regulation by p53 are distinctly affected during evolution. Importantly, gene up-regulation by p53 underwent more rapid evolution and gene down-regulation has been evolutionarily constrained. This difference stems from the two major mechanisms employed by p53 to regulate gene expression: up-regulation through direct p53 target gene binding and indirect down-regulation through the p53-p21-DREAM pathway. More than 1000 genes have been identified to differ in their p53-dependent expression between mice and humans. Analysis of p53 gene expression profiles and p53 binding data reveal that turnover of p53 binding sites is the major mechanism underlying extensive variation in p53-dependent gene up-regulation. Only a core set of high-confidence genes appears to be directly regulated by p53 in both species. In contrast to up-regulation, p53-induced down-regulation is well conserved between mice and humans and controls cell cycle genes. Here a curated data set is provided that extends the previously established web-atlas at www.targetgenereg.org to assess the p53 response of any human gene of interest and its mouse ortholog. Taken together, the analysis reveals a limited translation potential from mouse models to humans for the p53 GRN.
| S-EPMC6755996 | biostudies-literature
Project description:Gene regulatory networks (GRNs) drive developmental and cellular differentiation, and variation in their architectures gives rise to morphological diversity. Pioneering studies in Aspergillus fungi, coupled with subsequent work in other filamentous fungi, have shown that the GRN governed by the BrlA, AbaA, and WetA proteins controls the development of the asexual fruiting body or conidiophore. A specific aspect of conidiophore development is the production of phialides, conidiophore structures that are under the developmental control of AbaA and function to repetitively generate spores. Fungal genome sequencing has revealed that some filamentous fungi lack abaA, and also produce asexual structures that lack phialides, raising the hypothesis that abaA loss is functionally linked to diversity in asexual fruiting body morphology. To examine this hypothesis, we carried out an extensive search for the abaA gene across 241 genomes of species from the fungal subphylum Pezizomycotina. We found that abaA was independently lost in four lineages of Eurotiomycetes, including from all sequenced species within the order Onygenales, and that all four lineages that have lost abaA also lack the ability to form phialides. Genetic restoration of abaA from Aspergillus nidulans into Histoplasma capsulatum, a pathogenic species from the order Onygenales that lacks an endogenous copy of abaA, did not alter Histoplasma conidiation morphology but resulted in a marked increase in spore viability. We also discovered that species lacking abaA contain fewer AbaA binding motifs in the regulatory regions of orthologs of some AbaA target genes, suggesting that the asexual fruiting body GRN of organisms that have lost abaA has likely been rewired. Our results provide an illustration of how repeated losses of a key regulatory transcription factor have contributed to the diversity of an iconic fungal morphological trait.
| S-EPMC7531577 | biostudies-literature
Project description:The transition from vegetative growth to reproductive development is a complex process that requires an integrated response to multiple environmental cues and endogenous signals. In Arabidopsis thaliana, which has a facultative requirement for vernalization and long days, the genes of the autonomous pathway function as floral promoters by repressing the central repressor and vernalization-regulatory gene FLC. Environmental regulation by seasonal changes in daylength is under control of the photoperiod pathway and its key gene CO. The root and leaf crop species Beta vulgaris in the caryophyllid clade of core eudicots, which is only very distantly related to Arabidopsis, is an obligate long-day plant and includes forms with or without vernalization requirement. FLC and CO homologues with related functions in beet have been identified, but the presence of autonomous pathway genes which function in parallel to the vernalization and photoperiod pathways has not yet been reported. Here, this begins to be addressed by the identification and genetic mapping of full-length homologues of the RNA-regulatory gene FLK and the chromatin-regulatory genes FVE, LD, and LDL1. When overexpressed in A. thaliana, BvFLK accelerates bolting in the Col-0 background and fully complements the late-bolting phenotype of an flk mutant through repression of FLC. In contrast, complementation analysis of BvFVE1 and the presence of a putative paralogue in beet suggest evolutionary divergence of FVE homologues. It is further shown that BvFVE1, unlike FVE in Arabidopsis, is under circadian clock control. Together, the data provide first evidence for evolutionary conservation of components of the autonomous pathway in B. vulgaris, while also suggesting divergence or subfunctionalization of one gene. The results are likely to be of broader relevance because B. vulgaris expands the spectrum of evolutionarily diverse species which are subject to differential developmental and/or environmental regulation of floral transition.
| S-EPMC3130164 | biostudies-literature
Project description:Cleavage factor I (CFI) proteins are core components of the polyadenylation machinery that can regulate several steps of mRNA life cycle, including alternative polyadenylation, splicing, export and decay. Here, we describe the regulatory mechanisms that control two fungal CFI protein classes in Magnaporthe oryzae: Rbp35/CfI25 complex and Hrp1. Using mutational, genetic and biochemical studies we demonstrate that cellular concentration of CFI mRNAs is a limited indicator of their protein abundance. Our results suggest that several post-transcriptional mechanisms regulate Rbp35/CfI25 complex and Hrp1 in the rice blast fungus, some of which are also conserved in other ascomycetes. With respect to Rbp35, these include C-terminal processing, RGG-dependent localization and cleavage, C-terminal autoregulatory domain and regulation by an upstream open reading frame of Rbp35-dependent TOR signalling pathway. Our proteomic analyses suggest that Rbp35 regulates the levels of proteins involved in melanin and phenylpropanoids synthesis, among others. The drastic reduction of fungal CFI proteins in carbon-starved cells suggests that the pre-mRNA processing pathway is altered. Our findings uncover broad and multilayer regulatory mechanisms controlling fungal polyadenylation factors, which have profound implications in pre-mRNA maturation. This area of research offers new avenues for fungicide design by targeting fungal-specific proteins that globally affect thousands of mRNAs.
| S-EPMC4288187 | biostudies-other
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-09 | E-GEOD-58337 | biostudies-arrayexpress