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Differentially expressed genes in absence of histone H3K4 methyltransferase Set1 in Candida albicans

ABSTRACT: Candida albicans is an opportunistic human fungal pathogen. It exists as a member of human normal flora but can cause infection in immunocompromised individuals. Transition to pathogenic C. albicans requires a change in gene expression of various genes. As the histone-modifying enzymes can regulate gene expression, they can be considered as a factor controlling the virulence of C. albicans. Among them, it has been reported that the absence of H3K4 methyltransferase Set1 reduces the virulence of C. albicans. However, Set1-regulated genes responsible for this attenuated virulence phenotype are unknown. Here, we identified that the Set1 positively regulates the expression of mitochondrial protein genes and oxidative stress response-related genes through the methylation of H3K4. Levels of cellular mitochondrial reactive oxygen species (ROS) in Δset1 are also higher than those in the wild-type. Furthermore, Set1 deletion increases sensitivity to hydrogen peroxide (H2O2). Set1 deleted mutant also does not form its colony properly when it interacts with macrophage in vitro, in agreement with its attenuated virulence in vivo. Therefore, Set1 is required to inhibit cellular ROS production by positive regulation of mitochondrial protein genes and oxidative stress response-related genes expression, and consequently, the Set1-mediated gene expression assists C. albicans in defending against ROS generated from the host more rapidly.

ORGANISM(S): Candida albicans

PROVIDER: GSE158481 | GEO | 2021/11/03

REPOSITORIES: GEO

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H3K4 methylation regulates development, DNA repair, and virulence in Mucorales

Project description:Mucorales are basal fungi that opportunistically cause a fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic organisms. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.

2024-03-20 | GSE233894 | GEO

Transcriptional regulation by Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase

Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. To further understand the role for H3K4 methylation, we overexpressed Flag epitope-tagged SET1-G990E (a dominant hyperactive allele of SET1) in yeast using the constitutive ADH1 promoter (ADH1p). As a control, we also overexpressed Flag epitope-tagged wild type SET1 in yeast. Analysis of gene expression in set1-null, jhd2-null and wild type SET1 or hypeactive SET1-G990E overexpressing mutants together revealed that the transcriptional regulation at a sub-set of genes, inclduing those governing glycogen metabolism and ribosome biogenesis, is highly sensitive to any change (i.e., loss or gain) in H3K4 methylation levels. Overall, we find combined activities of Set1 and Jhd2 via dynamic modulation of H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes.

2016-06-15 | GSE73406 | GEO

Transcriptional regulation by Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase

2016-06-15 | E-GEOD-73406 | biostudies-arrayexpress

Differentially expressed genes in absence of histone H3K4 methyltransferase Set1 in Candida albicans

Project description:Differentially expressed genes in absence of histone H3K4 methyltransferase Set1 in Candida albicans

| PRJNA665387 | ENA

The Set1 N-terminal domain and Swd2 interact with the RNA polymerase II CTD to recruit COMPASS

Project description:Methylation of histone H3 lysine 4 (H3K4) by the Set1/COMPASS complex is coupled with active transcription, and this modification is important for regulating gene expression. Set1/COMPASS associates with the RNA polymerase II (RNApII) C-terminal domain (CTD) to establish proper levels and distribution of H3K4 methylations.To ask how the Set1-RNApII CTD binding affects the occupancy and overall level of H3K4 methylations, ChIP-Seq was pefromed in cells transformed with full length or N-terminal truncated Set1. Our results indicate that Set1-RNApII CTD interaction is necessary for maintaining H3K4 methylations throughout the genes.

2019-10-02 | GSE138281 | GEO

Regulation of chromatin structure by Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase [ChIP-seq]

Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylation−demethylation control chromatin dynamics during various facets of transcriptional regulation.

2016-06-15 | GSE81022 | GEO

Regulation of chromatin structure by Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase [histone turnover]

Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylation−demethylation control chromatin dynamics during various facets of transcriptional regulation.

2016-06-15 | GSE81021 | GEO

Regulation of chromatin structure by Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase [H3K4me ChIP-seq]

Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylation−demethylation control chromatin dynamics during various facets of transcriptional regulation.

2016-06-15 | GSE81020 | GEO

Regulation of chromatin structure by Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase

Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylation−demethylation control chromatin dynamics during various facets of transcriptional regulation.

2016-06-15 | GSE73404 | GEO

Regulation of chromatin structure by Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase

Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylationâdemethylation control chromatin dynamics during various facets of transcriptional regulation. Genome-wide nucleosome maps were generated from three different yeast strains representing wild type control, set1 null and jhd2 null mutants. Three independent biological samples were grown for each strain, nucleosomes were prepared by micrococcal nuclease digestion, libraries were prepared, mononculeosomal DNA was isolated, sequenced, and analyzed separately.

2016-06-15 | E-GEOD-73404 | biostudies-arrayexpress

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