The Experts below are selected from a list of 1875 Experts worldwide ranked by ideXlab platform
Susan K. Crosthwaite - One of the best experts on this subject based on the ideXlab platform.
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neurospora crassa heat shock factor 1 is an essential gene a second heat shock factor like gene hsf2 is required for Asexual Spore formation
Eukaryotic Cell, 2008Co-Authors: Seona Thompson, Nirvana J Croft, Antonis Sotiriou, Hugh D. Piggins, Susan K. CrosthwaiteAbstract:Appropriate responses of organisms to heat stress are essential for their survival. In eukaryotes, adaptation to high temperatures is mediated by heat shock transcription factors (HSFs). HSFs regulate the expression of heat shock proteins, which function as molecular chaperones assisting in protein folding and stability. In many model organisms a great deal is known about the products of hsf genes. An important exception is the filamentous fungus and model eukaryote Neurospora crassa. Here we show that two Neurospora crassa genes whose protein products share similarity to known HSFs play different biological roles. We report that heat shock factor 1 (hsf1) is an essential gene and that hsf2 is required for Asexual development. Conidiation may be blocked in the hsf2 knockout (hsf2KO) strain because HSF2 is an integral element of the conidiation pathway or because it affects the availability of protein chaperones. We report that genes expressed during conidiation, for example fluffy, conidiation-10, and repressor of conidiation-1 show wild-type levels of expression in a hsf2KO strain. However, consistent with the lack of macroconidium development, levels of eas are much reduced. Cultures of the hsf2KO strain along with two other aconidial strains, the fluffy and aconidial-2 strains, took longer than the wild type to recover from heat shock. Altered expression profiles of hsp90 and a putative hsp90-associated protein in the hsf2KO strain after exposure to heat shock may in part account for its reduced ability to cope with heat stress.
Seona Thompson - One of the best experts on this subject based on the ideXlab platform.
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neurospora crassa heat shock factor 1 is an essential gene a second heat shock factor like gene hsf2 is required for Asexual Spore formation
Eukaryotic Cell, 2008Co-Authors: Seona Thompson, Nirvana J Croft, Antonis Sotiriou, Hugh D. Piggins, Susan K. CrosthwaiteAbstract:Appropriate responses of organisms to heat stress are essential for their survival. In eukaryotes, adaptation to high temperatures is mediated by heat shock transcription factors (HSFs). HSFs regulate the expression of heat shock proteins, which function as molecular chaperones assisting in protein folding and stability. In many model organisms a great deal is known about the products of hsf genes. An important exception is the filamentous fungus and model eukaryote Neurospora crassa. Here we show that two Neurospora crassa genes whose protein products share similarity to known HSFs play different biological roles. We report that heat shock factor 1 (hsf1) is an essential gene and that hsf2 is required for Asexual development. Conidiation may be blocked in the hsf2 knockout (hsf2KO) strain because HSF2 is an integral element of the conidiation pathway or because it affects the availability of protein chaperones. We report that genes expressed during conidiation, for example fluffy, conidiation-10, and repressor of conidiation-1 show wild-type levels of expression in a hsf2KO strain. However, consistent with the lack of macroconidium development, levels of eas are much reduced. Cultures of the hsf2KO strain along with two other aconidial strains, the fluffy and aconidial-2 strains, took longer than the wild type to recover from heat shock. Altered expression profiles of hsp90 and a putative hsp90-associated protein in the hsf2KO strain after exposure to heat shock may in part account for its reduced ability to cope with heat stress.
Antonis Rokas - One of the best experts on this subject based on the ideXlab platform.
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Systematic Dissection of the Evolutionarily Conserved WetA Developmental Regulator across a Genus of Filamentous Fungi.
mBio, 2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Erin M Ostrem Loss, Antonis RokasAbstract:ABSTRACT Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA→AbaA→WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and governs not only the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses of comparisons between wetA null mutant and wild-type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and 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, data from chromatin immunoprecipitation sequencing (ChIP-seq) experiments in A. nidulans Asexual Spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA→AbaA→WetA cascade’s regulatory role in cellular and chemical Asexual Spore development is functionally conserved but that the wetA-associated GRN has diverged during Aspergillus evolution. IMPORTANCE The formation of resilient Spores is a key factor contributing to the survival and fitness of many microorganisms, including fungi. In the fungal genus Aspergillus, Spore formation is controlled by a complex gene regulatory network that also impacts a variety of other processes, including secondary metabolism. To gain mechanistic insights into how fungal Spore formation is controlled across Aspergillus, we dissected the gene regulatory network downstream of a major regulator of Spore maturation (WetA) in three species that span the diversity of the genus: the genetic model A. nidulans, the human pathogen A. fumigatus, and the aflatoxin producer A. flavus. Our data show that WetA regulates Asexual sporulation in all three species via a negative-feedback loop and likely binds a novel regulatory element that we term the WetA response element (WRE). These results shed light on how gene regulatory networks in microorganisms control important biological processes and evolve across diverse species.
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Conservation and Divergence in the Asexual Sporulation Gene Regulatory Network Across a Genus of Filamentous Fungi
2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Antonis RokasAbstract:Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA->AbaA->WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and not only governs the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remains largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and A. fumigatus. We discovered that WetA regulates Asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascade9s 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 motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA->AbaA->WetA cascade9s regulatory role in cellular and chemical Asexual Spore development is functionally conserved, but that the wetA-associated GRN has diverged during Aspergillus evolution.
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Systematic Dissection of the Evolutionarily Conserved WetA Developmental Regulator across a Genus of Filamentous Fungi
American Society for Microbiology, 2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Erin M Ostrem Loss, Antonis RokasAbstract:Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA→AbaA→WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and governs not only the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses of comparisons between wetA null mutant and wild-type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and 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, data from chromatin immunoprecipitation sequencing (ChIP-seq) experiments in A. nidulans Asexual Spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA→AbaA→WetA cascade’s regulatory role in cellular and chemical Asexual Spore development is functionally conserved but that the wetA-associated GRN has diverged during Aspergillus evolution.The formation of resilient Spores is a key factor contributing to the survival and fitness of many microorganisms, including fungi. In the fungal genus Aspergillus, Spore formation is controlled by a complex gene regulatory network that also impacts a variety of other processes, including secondary metabolism. To gain mechanistic insights into how fungal Spore formation is controlled across Aspergillus, we dissected the gene regulatory network downstream of a major regulator of Spore maturation (WetA) in three species that span the diversity of the genus: the genetic model A. nidulans, the human pathogen A. fumigatus, and the aflatoxin producer A. flavus. Our data show that WetA regulates Asexual sporulation in all three species via a negative-feedback loop and likely binds a novel regulatory element that we term the WetA response element (WRE). These results shed light on how gene regulatory networks in microorganisms control important biological processes and evolve across diverse species
Matthew E. Mead - One of the best experts on this subject based on the ideXlab platform.
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Transcriptomic, protein-DNA interaction, and metabolomic studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores
2020Co-Authors: Matthew E. Mead, Ye-eun Son, Mi-kyung Lee, George F. Neuhaus, Donovon A. Adpressa, Julia Martien, Heungyun Moon, Daniel Amador-noguez, Kap-hoon HanAbstract:Abstract In filamentous fungi, Asexual development involves morphological differentiation and metabolic changes leading to the formation of Asexual Spores. The process of Asexual Spore formation in Aspergillus is precisely regulated by multiple transcription factors (TFs), including VosA, VelB, and WetA, and these three TFs are key regulators of the formation and maturation of Asexual Spores (conidia) in Aspergillus including the model fungus Aspergillus nidulans. To gain a mechanistic insight on the complex regulatory roles of these TFs in Asexual Spores, we conducted genome-wide studies on the expression, protein-DNA interactions, and primary and secondary metabolism employing A. nidulans conidia. RNA sequencing and chromatin immunoprecipitation-sequencing data have revealed that the three TFs directly or indirectly regulate the expression of genes associated with Spore-wall formation/integrity, Asexual development, and secondary metabolism. In addition, metabolomics analyses of wild-type and mutant conidia indicate that these three TFs regulate a diverse array of primary and secondary metabolism. In summary, WetA, VosA, and VelB play inter-dependent and distinct roles governing morphological development and primary/secondary metabolic remodeling in Aspergillus conidia. Importance Filamentous fungi produce a vast number of Asexual Spores that act as reproductive and propagator cells. These Spores affect humans, due to the infectious or allergenic nature of the propagule. Aspergillus species produce Asexual Spores called conidia and their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by Spore-specific transcription factors. To understand the underlying global regulatory programs and cellular outcomes associated with conidia formation, functional genomic and metabolomic analyses were performed in the model fungus Aspergillus nidulans. Our results show that the fungus specific WetA/VosA/VelB transcription factors govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the genetic regulatory networks about how morphological developments and metabolic changes are coordinated in fungi. The findings are relevant for other Aspergillus species such as the major human pathogen Aspergillus fumigatus and the aflatoxin-producer Aspergillus flavus.
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Systematic Dissection of the Evolutionarily Conserved WetA Developmental Regulator across a Genus of Filamentous Fungi.
mBio, 2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Erin M Ostrem Loss, Antonis RokasAbstract:ABSTRACT Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA→AbaA→WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and governs not only the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses of comparisons between wetA null mutant and wild-type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and 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, data from chromatin immunoprecipitation sequencing (ChIP-seq) experiments in A. nidulans Asexual Spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA→AbaA→WetA cascade’s regulatory role in cellular and chemical Asexual Spore development is functionally conserved but that the wetA-associated GRN has diverged during Aspergillus evolution. IMPORTANCE The formation of resilient Spores is a key factor contributing to the survival and fitness of many microorganisms, including fungi. In the fungal genus Aspergillus, Spore formation is controlled by a complex gene regulatory network that also impacts a variety of other processes, including secondary metabolism. To gain mechanistic insights into how fungal Spore formation is controlled across Aspergillus, we dissected the gene regulatory network downstream of a major regulator of Spore maturation (WetA) in three species that span the diversity of the genus: the genetic model A. nidulans, the human pathogen A. fumigatus, and the aflatoxin producer A. flavus. Our data show that WetA regulates Asexual sporulation in all three species via a negative-feedback loop and likely binds a novel regulatory element that we term the WetA response element (WRE). These results shed light on how gene regulatory networks in microorganisms control important biological processes and evolve across diverse species.
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Conservation and Divergence in the Asexual Sporulation Gene Regulatory Network Across a Genus of Filamentous Fungi
2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Antonis RokasAbstract:Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA->AbaA->WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and not only governs the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remains largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and A. fumigatus. We discovered that WetA regulates Asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascade9s 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 motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA->AbaA->WetA cascade9s regulatory role in cellular and chemical Asexual Spore development is functionally conserved, but that the wetA-associated GRN has diverged during Aspergillus evolution.
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Systematic Dissection of the Evolutionarily Conserved WetA Developmental Regulator across a Genus of Filamentous Fungi
American Society for Microbiology, 2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Erin M Ostrem Loss, Antonis RokasAbstract:Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA→AbaA→WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and governs not only the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses of comparisons between wetA null mutant and wild-type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and 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, data from chromatin immunoprecipitation sequencing (ChIP-seq) experiments in A. nidulans Asexual Spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA→AbaA→WetA cascade’s regulatory role in cellular and chemical Asexual Spore development is functionally conserved but that the wetA-associated GRN has diverged during Aspergillus evolution.The formation of resilient Spores is a key factor contributing to the survival and fitness of many microorganisms, including fungi. In the fungal genus Aspergillus, Spore formation is controlled by a complex gene regulatory network that also impacts a variety of other processes, including secondary metabolism. To gain mechanistic insights into how fungal Spore formation is controlled across Aspergillus, we dissected the gene regulatory network downstream of a major regulator of Spore maturation (WetA) in three species that span the diversity of the genus: the genetic model A. nidulans, the human pathogen A. fumigatus, and the aflatoxin producer A. flavus. Our data show that WetA regulates Asexual sporulation in all three species via a negative-feedback loop and likely binds a novel regulatory element that we term the WetA response element (WRE). These results shed light on how gene regulatory networks in microorganisms control important biological processes and evolve across diverse species
Mi-kyung Lee - One of the best experts on this subject based on the ideXlab platform.
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Transcriptomic, protein-DNA interaction, and metabolomic studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores
2020Co-Authors: Matthew E. Mead, Ye-eun Son, Mi-kyung Lee, George F. Neuhaus, Donovon A. Adpressa, Julia Martien, Heungyun Moon, Daniel Amador-noguez, Kap-hoon HanAbstract:Abstract In filamentous fungi, Asexual development involves morphological differentiation and metabolic changes leading to the formation of Asexual Spores. The process of Asexual Spore formation in Aspergillus is precisely regulated by multiple transcription factors (TFs), including VosA, VelB, and WetA, and these three TFs are key regulators of the formation and maturation of Asexual Spores (conidia) in Aspergillus including the model fungus Aspergillus nidulans. To gain a mechanistic insight on the complex regulatory roles of these TFs in Asexual Spores, we conducted genome-wide studies on the expression, protein-DNA interactions, and primary and secondary metabolism employing A. nidulans conidia. RNA sequencing and chromatin immunoprecipitation-sequencing data have revealed that the three TFs directly or indirectly regulate the expression of genes associated with Spore-wall formation/integrity, Asexual development, and secondary metabolism. In addition, metabolomics analyses of wild-type and mutant conidia indicate that these three TFs regulate a diverse array of primary and secondary metabolism. In summary, WetA, VosA, and VelB play inter-dependent and distinct roles governing morphological development and primary/secondary metabolic remodeling in Aspergillus conidia. Importance Filamentous fungi produce a vast number of Asexual Spores that act as reproductive and propagator cells. These Spores affect humans, due to the infectious or allergenic nature of the propagule. Aspergillus species produce Asexual Spores called conidia and their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by Spore-specific transcription factors. To understand the underlying global regulatory programs and cellular outcomes associated with conidia formation, functional genomic and metabolomic analyses were performed in the model fungus Aspergillus nidulans. Our results show that the fungus specific WetA/VosA/VelB transcription factors govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the genetic regulatory networks about how morphological developments and metabolic changes are coordinated in fungi. The findings are relevant for other Aspergillus species such as the major human pathogen Aspergillus fumigatus and the aflatoxin-producer Aspergillus flavus.
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Homeobox proteins are essential for fungal differentiation and secondary metabolism in Aspergillus nidulans.
Scientific Reports, 2020Co-Authors: Sung-hun Son, Ye-eun Son, He-jin Cho, Wanping Chen, Mi-kyung Lee, Lee-han Kim, Dong-min Han, Hee-soo ParkAbstract:The homeobox domain-containing transcription factors play an important role in the growth, development, and secondary metabolism in fungi and other eukaryotes. In this study, we characterized the roles of the genes coding for homeobox-type proteins in the model organism Aspergillus nidulans. To examine their roles in A. nidulans, the deletion mutant strains for each gene coding for homeobox-type protein were generated, and their phenotypes were examined. Phenotypic analyses revealed that two homeobox proteins, HbxA and HbxB, were required for conidia production. Deletion of hbxA caused abnormal conidiophore production, decreased the number of conidia in both light and dark conditions, and decreased the size of cleistothecia structures. Overexpressing hbxA enhanced the production of Asexual Spores and formation of conidiophore under the liquid submerged conditions. The hbxB deletion mutant strains exhibited decreased Asexual Spore production but increased cleistothecia production. The absence of hbxB decreased the trehalose content in Asexual Spores and increased their sensitivity against thermal and oxidative stresses. The ΔhbxA strains produced more sterigmatocystin, which was decreased in the ΔhbxB strain. Overall, our results show that HbxA and HbxB play crucial roles in the differentiation and secondary metabolism of the fungus A. nidulans.
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Systematic Dissection of the Evolutionarily Conserved WetA Developmental Regulator across a Genus of Filamentous Fungi.
mBio, 2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Erin M Ostrem Loss, Antonis RokasAbstract:ABSTRACT Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA→AbaA→WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and governs not only the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses of comparisons between wetA null mutant and wild-type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and 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, data from chromatin immunoprecipitation sequencing (ChIP-seq) experiments in A. nidulans Asexual Spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA→AbaA→WetA cascade’s regulatory role in cellular and chemical Asexual Spore development is functionally conserved but that the wetA-associated GRN has diverged during Aspergillus evolution. IMPORTANCE The formation of resilient Spores is a key factor contributing to the survival and fitness of many microorganisms, including fungi. In the fungal genus Aspergillus, Spore formation is controlled by a complex gene regulatory network that also impacts a variety of other processes, including secondary metabolism. To gain mechanistic insights into how fungal Spore formation is controlled across Aspergillus, we dissected the gene regulatory network downstream of a major regulator of Spore maturation (WetA) in three species that span the diversity of the genus: the genetic model A. nidulans, the human pathogen A. fumigatus, and the aflatoxin producer A. flavus. Our data show that WetA regulates Asexual sporulation in all three species via a negative-feedback loop and likely binds a novel regulatory element that we term the WetA response element (WRE). These results shed light on how gene regulatory networks in microorganisms control important biological processes and evolve across diverse species.
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Conservation and Divergence in the Asexual Sporulation Gene Regulatory Network Across a Genus of Filamentous Fungi
2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Antonis RokasAbstract:Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA->AbaA->WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and not only governs the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remains largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and A. fumigatus. We discovered that WetA regulates Asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascade9s 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 motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA->AbaA->WetA cascade9s regulatory role in cellular and chemical Asexual Spore development is functionally conserved, but that the wetA-associated GRN has diverged during Aspergillus evolution.
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Systematic Dissection of the Evolutionarily Conserved WetA Developmental Regulator across a Genus of Filamentous Fungi
American Society for Microbiology, 2018Co-Authors: Matthew E. Mead, Mi-kyung Lee, Sun Chang Kim, Erin M Ostrem Loss, Antonis RokasAbstract:Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of Asexual Spores is primarily governed by the BrlA→AbaA→WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and governs not only the morphological differentiation of Spores but also the production and deposition of diverse metabolites into Spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses of comparisons between wetA null mutant and wild-type Asexual Spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and 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, data from chromatin immunoprecipitation sequencing (ChIP-seq) experiments in A. nidulans Asexual Spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge Spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA→AbaA→WetA cascade’s regulatory role in cellular and chemical Asexual Spore development is functionally conserved but that the wetA-associated GRN has diverged during Aspergillus evolution.The formation of resilient Spores is a key factor contributing to the survival and fitness of many microorganisms, including fungi. In the fungal genus Aspergillus, Spore formation is controlled by a complex gene regulatory network that also impacts a variety of other processes, including secondary metabolism. To gain mechanistic insights into how fungal Spore formation is controlled across Aspergillus, we dissected the gene regulatory network downstream of a major regulator of Spore maturation (WetA) in three species that span the diversity of the genus: the genetic model A. nidulans, the human pathogen A. fumigatus, and the aflatoxin producer A. flavus. Our data show that WetA regulates Asexual sporulation in all three species via a negative-feedback loop and likely binds a novel regulatory element that we term the WetA response element (WRE). These results shed light on how gene regulatory networks in microorganisms control important biological processes and evolve across diverse species