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Global proteome analysis of conditional sth1 mutant in Candida albicans

ABSTRACT: Regulation of gene expression programs is crucial for the survival of microbial pathogens in host environments and for their ability to cause disease. Here we investigated the epigenetic regulator RSC (Remodels the Structure of Chromatin) in the most prevalent human fungal pathogen Candida albicans. We addressed the global functions of RSC in C. albicans by analyzing the changes in the proteome of cells lacking the catalytic subunit Sth1 using DIA-MS (Data Independent Acquisition-Mass Spectrometry). For this purpose, we generated a conditional mutant harboring a doxycycline (dox)-repressible allele of STH1 (sth1∆/pTetO-STH1-MYC) and treated this mutant with dox for Sth1 depletion. To assess the effect of dox alone on gene expression, a near-isogenic sth1∆/STH1-MYC strain was also analysed.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Candida Albicans (yeast)

SUBMITTER: Vinutha K B

LAB HEAD: Santanu Kumar Ghosh

PROVIDER: PXD017990 | Pride | 2020-11-11

REPOSITORIES: Pride

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The RSC (Remodels the Structure of Chromatin) complex of Candida albicans shows compositional divergence with distinct roles in regulating pathogenic traits.

Balachandra Vinutha K VK Verma Jiyoti J Shankar Madhu M Tucey Timothy M TM Traven Ana A Schittenhelm Ralf B RB Ghosh Santanu K SK

PLoS genetics 20201105 11

Regulation of gene expression programs is crucial for the survival of microbial pathogens in host environments and for their ability to cause disease. Here we investigated the epigenetic regulator RSC (Remodels the Structure of Chromatin) in the most prevalent human fungal pathogen Candida albicans. Biochemical analysis showed that CaRSC comprises 13 subunits and contains two novel non-essential members, which we named Nri1 and Nri2 (Novel RSC Interactors) that are exclusive to the CTG clade of ...[more]

PMID: 33151931

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Validation of Nri1/Nri2 physical interaction with the Candida albicans RSC complex

2020-11-11 | PXD017987 | Pride

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2020-11-11 | PXD017988 | Pride

The RSC (Remodels the Structure of Chromatin) complex of Candida albicans shows compositional divergence and plays distinct roles in regulating pathogenic traits

Project description:Regulation of gene expression programs is crucial for the survival of microbial pathogens in host environments and for their ability to cause disease. Here we investigated the epigenetic regulator RSC (Remodels the Structure of Chromatin) in the most prevalent human fungal pathogen Candida albicans. Biochemical analysis showed that CaRSC comprises 13 subunits and contains two novel non-essential members, which we named Nri1 and Nri2 (Novel RSC Interactors) that are exclusive to the CTG clade of Saccharomycotina. Genetic analysis showed distinct essentiality of C. albicans RSC subunits compared to model fungal species suggesting functional and structural divergence of RSC functions in this fungal pathogen. Transcriptomic and proteomic profiling of a conditional mutant of the essential catalytic subunit STH1 demonstrated global roles of RSC in C. albicans biology, with the majority of growth-related processes affected, as well as mis-regulation of genes involved in morphotype switching, host-pathogen interaction and adaptive fitness. We further assessed the functions of non-essential CaRSC subunits, showing that the novel subunit Nri1 and the bromodomain subunit Rsc4 play roles in filamentation and stress responses; and also interacted at the genetic level to regulate cell viability. Consistent with these roles, Rsc4 is required for full virulence of C. albicans in the murine model of systemic infection. Taken together, our data builds the first comprehensive study of the composition and roles of RSC in C. albicans, showing conserved and distinct features compared to model fungal systems, and illuminating how C. albicans uses RSC-dependent transcriptional regulation to respond to environmental signals and drive fitness and virulence in mammals.

2020-11-19 | GSE145831 | GEO

c-Myc uses Cul4b to preserve genome stability and promote CD8+ T cell-mediated antiviral immune responses

Project description:During infection, virus-specific CD8+ T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. We found that c-Myc utilizes the E3 ubiquitin ligase, Cul4b, to inextricably link CD8+ T cell expansion to DNA damage response pathways. Following activation, c-Myc increased levels of Cul4b and other members of the CRL4 complex. Despite having abundant c-Myc expression, Cul4b-deficient CD8+ T cells were unable to expand and clear virus. Cul4b-deficient CD8+ T cells accrued DNA damage and succumbed to proliferative catastrophe early after antigen encounter. Mechanistically, Cul4b ablation induced a protracted accumulation of p21 and Cyclin E2 resulting in replication stress. Our data show that, to support cell proliferation, c-Myc must employ Cul4b to maintain genome stability, thereby directly coupling these two interdependent pathways. These data clarify how CD8+ T cells use c-Myc and Cul4b to sustain their potential for extraordinary population expansion, longevity and antiviral responses.

2023-08-29 | PXD041220 | Pride

A unique iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis [ChIP_chip]

Project description:The mammalian gastrointestinal tract and the bloodstream are highly disparate biological niches, and yet certain commensal-pathogenic microorganisms are able to thrive in both environments. Here, we report the evolution of a unique transcription circuit in the yeast, Candida albicans, which determines its fitness in both host niches. Our comprehensive analysis of the DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved transcriptional repressors, Sfu1 and Hap43. The Sef1 activator of iron uptake genes promotes virulence in a mouse model of bloodstream infection, whereas the Sfu1 repressor is dispensable for virulence but promotes gastrointestinal commensalism. We propose that the ability to alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut may be a fundamental attribute of gastrointestinal commensal-pathogens. ChIP analyses to profile genome-wide of distribution of Sef1, Sfu1 and Hap43 in response to various iron availability. 12 independent ChIP experiments were performed on 6 biological replicates of the untagged control and 2 biological replicates each of Sef1-Myc, Sfu1-Myc, and Hap43-Myc.

2011-07-12 | E-GEOD-30591 | biostudies-arrayexpress

Chromatin occupancy of key transcriptional regulators in P493-6 cells with various levels of c-Myc expression

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2012-11-14 | E-GEOD-42262 | biostudies-arrayexpress

Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX

Project description:Idax/Cxxc4 is the CXXC domain protein that preferentially binds unmethylated CpG sites in vitro. By performing genome-wide mapping of Idax/Cxxc4, we report here that Idax is preferentially enriched in CpG-rich regions in genome including the promoters containing CpG islands. ChIP-seq binding site detection of Myc-Idax and Myc-IdaxDBM over cells expressing an empty vector in stable HEK293T cell lines; two replicates per condition (2x ChIP Myc-Idax, 2x ChIP Myc-IdaxDBM, 2xChIP empty vector)

2013-04-03 | E-GEOD-42958 | biostudies-arrayexpress

A Myc-mediated dormant state of naive ESCs

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2016-02-11 | E-MTAB-3386 | biostudies-arrayexpress

The APSES Transcription factor Efg1 regulates a novel phenotype switch in Candida parapsilosis [ChIP-seq].

Project description:We use ChIP-seq to identify the targets of Efg1 in Candida parapsilosis. We show that Efg1 binds to 502 promoter regions, including 70 potential transcription factors or regulatory proteins. Several of the transcription factors belong to networks that regulate biofilm development and white-opaque switching in C. albicans. Efg1 also binds to its own promoter. The binding site for C. parapsilosis Efg1 resembles that of orthologs in other fungi. Many Efg1 targets are probably also regulated by the Ndt80 transcription factor. Efg1 in C. parapsilosis was tagged in situ using a myc epitope. Examination of Efg1-myc DNA binding sites by ChIP-seq. Three immunoprecipitated samples were sequenced and three input samples (pre-immunoprecipitation) were sequenced as controls.

2013-06-20 | E-GEOD-41063 | biostudies-arrayexpress

Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis [ChIP-Seq]

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2014-07-07 | E-GEOD-51004 | biostudies-arrayexpress

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