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Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Cryptococcus neoformans var. grubii H99

PROVIDER: GSE135040 | GEO | 2020/09/01

REPOSITORIES: GEO

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Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans (ChIP-seq)

Project description:Purpose: Defining the regulatory role of the transcription factor Sre1 in C. neoformans. Methods: Chromatin immunoprecipitation followed by high-throughput sequencing was performed using chromatin immunoprecipitated DNA from the strain Flag-Sre1 grown in low- and high-iron media under normoxia and hypoxia condition. Results: Sre1 directly bind to the promoter region of the genes involved in ergosterol biosynthetic pathway and iron acquisition in C. neoformans.

2020-09-01 | GSE135038 | GEO

Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans (RNA-seq)

Project description:Purpose: Understanding the regulatory role of Sre1 in Cryptococcus neoformans. Methods: The transcriptome profiles of the wild-type and sre1 mutant were generated by RNA-seq using Illumina Hiseq. The transcriptome profile of the sre1 mutant was compared with that of the wild-type strain. Results: The Sterol Regulatory Element Binding Protein, Sre1 is a major regulator for the genes involved in ergosterol biosynthetic pathway and iron acquisition in C. neoformans.

2020-09-01 | GSE135039 | GEO

Conservation of the sterol regulatory element-binding protein pathway and its pathobiological importance in Cryptococcus neoformans.

Project description:The mammalian sterol regulatory element-binding protein (SREBP) homolog, Sre1, is important for adaptation and growth of Cryptococcus neoformans in the mouse brain, where oxygen concentration and nutritional conditions are suboptimal for fungal growth. The extent of conservation of the SREBP pathway in C. neoformans or in any other fungi, however, has not been investigated. We generated mutants susceptible to low oxygen and identified six genes that play a role in the SREBP pathway. Three of these genes (SFB2, KAP123, and GSK3) are not known to be involved in the SREBP pathway in other fungi. Furthermore, we show that C. neoformans contains an additional gene, DAM1, which functions in the SREBP pathway but is yet to be described. Mutants associated with the steps prior to formation of the nuclear Sre1 form dramatically reduced accumulation of the nuclear form under low-oxygen conditions. Concurrently, two mutant strains, scp1Delta and stp1Delta, and the previously isolated sre1Delta strain showed reduction in ergosterol levels, hypersensitivity to several chemical agents, including azole antifungals, CoCl(2), and compounds producing reactive oxygen or nitrogen species, and most importantly, reduced virulence in mice. Mutants affecting genes involved in later steps of the Sre1 pathway, such as those required for import and phosphorylation of proteins in the nucleus, showed less compelling phenotypes. These findings suggest that the SREBP pathway is highly conserved in C. neoformans and it serves as an important link between sterol biosynthesis, oxygen sensing, CoCl(2) sensitivity, and virulence in C. neoformans.

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Sterol regulatory element-binding protein Sre1 regulates carotenogenesis in the red yeast <i>Xanthophyllomyces dendrorhous</i>.

Project description:Xanthophyllomyces dendrorhous is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. X. dendrorhous has a functional SREBP pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how sterol regulatory element (Sre)1 promotes the biosynthesis of sterols and carotenoids in X. dendrorhous is unknown. In this work, comparative RNA-sequencing analysis between modified X. dendrorhous strains that have an active Sre1 protein and the WT was performed to identify Sre1-dependent genes. In addition, Sre1 direct target genes were identified through ChIP combined with lambda exonuclease digestion (ChIP-exo) assays. SRE motifs were detected in the promoter regions of several Sre1 direct target genes and were consistent with the SREs described in other yeast species. Sre1 directly regulates genes related to ergosterol biosynthesis as well as genes related to the mevalonate (MVA) pathway, which synthesizes the building blocks of isoprenoids, including carotenoids. Two carotenogenic genes, crtE and crtR, were also identified as Sre1 direct target genes. Thus, carotenogenesis in X. dendrorhous is regulated by Sre1 through the regulation of the MVA pathway and the regulation of the crtE and crtR genes. As the crtR gene encodes a cytochrome P450 reductase, Sre1 regulates pathways that include cytochrome P450 enzymes, such as the biosynthesis of carotenoids and sterols. These results demonstrate that Sre1 is a sterol master regulator that is conserved in X. dendrorhous.

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Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in <i>Xanthophyllomyces dendrorhous</i>.

Project description:Xanthophyllomyces dendrorhous is a basidiomycete yeast that synthesizes carotenoids, mainly astaxanthin, which are of great commercial interest. Currently, there are many unknown aspects related to regulatory mechanisms on the synthesis of carotenoids in this yeast. Our recent studies showed that changes in sterol levels and composition resulted in upregulation of genes in the mevalonate pathway required for the synthesis of carotenoid precursors, leading to increased production of these pigments. Sterol Regulatory Element-Binding Proteins (SREBP), called Sre1 in yeast, are conserved transcriptional regulators of sterol homeostasis and other cellular processes. Given the results linking sterols and carotenoids, we investigated the role of SREBP in sterol and carotenoid synthesis in X. dendrorhous. In this study, we present the identification and functional characterization of the X. dendrorhous SRE1 gene, which encodes the transcription factor Sre1. The deduced protein has the characteristic features of SREBP/Sre1 and binds to consensus DNA sequences in vitro. RNA-seq analysis and chromatin-immunoprecipitation experiments showed that genes of the mevalonate pathway and ergosterol biosynthesis are directly regulated by Sre1. The sre1- mutation reduced sterol and carotenoid production in X. dendrorhous, and expression of the Sre1 N-terminal domain (Sre1N) increased carotenoid production more than twofold compared to wild-type. Overall, our results indicate that in X. dendrorhous transcriptional regulation of genes in the mevalonate pathway control production of the isoprenoid derivatives, carotenoids and sterol. Our results provide new insights into the conserved regulatory functions of SREBP/Sre1 and identify pointing to the SREBP pathway as a potential target to enhance carotenoid production in X. dendrorhous.

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Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans

Project description:Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans

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Sterol Regulatory Element-Binding Protein Sre1 regulates carotenogenesis in the red yeast Xanthophyllomyces dendrorhous.

Project description:Xanthophyllomyces dendrorhous is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. X. dendrorhous has a functional Sterol Regulatory Element-Binding Protein (SREBP) pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how Sre1 is promoting the biosynthesis of sterols and carotenoids in X. dendrorhous is unknown. In this work, comparative RNA-seq analysis between modified X. dendrorhous strains that have an active Sre1 protein and the wild-type was performed to identify Sre1-dependent genes. In addition, Sre1 direct target genes were identified through chromatin immunoprecipitation combined with lambda exonuclease digestion (ChIP-exo) assays. SRE motifs were detected in the promoter regions of several Sre1 direct target genes and were consistent with the SREs described in other yeast species. Sre1 directly regulates genes related to ergosterol biosynthesis as well as genes related to the mevalonate pathway, which synthesizes the building blocks of isoprenoids, including carotenoids. Two carotenogenic genes, crtE and crtR, were also identified as Sre1 direct target genes. Thus, carotenogenesis in X. dendrorhous is regulated by Sre1 through the regulation of the mevalonate pathway and the regulation of the crtE and crtR genes. As the crtR gene encodes a cytochrome P450 reductase, Sre1 regulates pathways that include cytochrome P450 enzymes, such as the biosynthesis of carotenoids and sterols. These results demonstrate that Sre1 is a sterol master regulator that is conserved in X. dendrorhous.

2020-09-29 | GSE152739 | GEO

Zinc Finger Proteins in the Human Fungal Pathogen Cryptococcus neoformans.

Project description:Zinc is one of the essential trace elements in eukaryotes and it is a critical structural component of a large number of proteins. Zinc finger proteins (ZNFs) are zinc-finger domain-containing proteins stabilized by bound zinc ions and they form the most abundant proteins, serving extraordinarily diverse biological functions. In recent years, many ZNFs have been identified and characterized in the human fungal pathogen Cryptococcus neoformans, a fungal pathogen causing fatal meningitis mainly in immunocompromised individuals. It has been shown that ZNFs play important roles in the morphological development, differentiation, and virulence of C. neoformans. In this review, we, first, briefly introduce the ZNFs and their classification. Then, we explain the identification and classification of the ZNFs in C. neoformans. Next, we focus on the biological role of the ZNFs functionally characterized so far in the sexual reproduction, virulence factor production, ion homeostasis, pathogenesis, and stress resistance in C. neoformans. We also discuss the perspectives on future function studies of ZNFs in C. neoformans.

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Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans (ChIP-seq)

Project description:Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans (ChIP-seq)

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Genome-wide analysis of a transcriptional network of the Sterol Regulatory Element Binding Protein, Sre1, in the human fungal pathogen Cryptococcus neoformans (RNA-seq)

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