The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence

Boukhaled, Giselle M.; Cordeiro, Brendan; Deblois, Geneviève; Dimitrov, V.; Bailey, Swneke D.; Holowka, Thomas; Domi, Anisa; Guak, Hannah; Chiu, Huai-Hsuan Clare; Everts, Bart; Pearce, Edward J.; Lupien, Mathieu; White, John H.; Krawczyk, Connie M.

doi:10.1016/j.celrep.2016.07.026

Cited by 34 publications

(39 citation statements)

References 36 publications

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“…To understand the differences in host response to SARS-CoV-2 infection, we tested the interaction between infection and age (greater than 60), controlling for non–infection-related age differences with SARS-CoV-2-negative samples. We found only 2 genes altered as a result of the interaction between age and SARS-CoV-2 infection: a 30-fold reduction in production of CXCL11 ( Fig 5B ), an interferon-induced chemokine for NK and CD8+ T cells, and a 17-fold reduction in polycomb group factor 6 ( PCGF6 ) ( S2A Fig ), a polycomb repressor complex protein known to play a role in repression of dendritic cell activation [ 31 ]. Although we did not find additional genes altered specifically as a result of age in SARS-CoV-2 infection, we did find that CXCL9 and C XCL10 are not induced as strongly in SARS-CoV-2-positive patients aged 60 or older.…”

Section: Resultsmentioning

confidence: 99%

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

et al. 2020

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Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) swabs from 430 individuals with PCRconfirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with up-regulation of antiviral factors such as OAS1-3 and IFIT1-3 and T helper type 1 (Th1) chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial (HAE) cultures replicated the in vivo antiviral host response 7 days post infection, with no induction of interferon-stimulated genes after 3 days. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of the Th1 chemokines CXCL9/10/11 and their cognate receptor CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B cell-specific and NK cell-specific transcripts and an increase in inhibitors of nuclear factor kappa-B (NF-κB) signaling, possibly

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Section: Resultsmentioning

confidence: 99%

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

et al. 2020

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“…Nevertheless, our research showed that only Pcgf6 was both differentially mutated and closely linked to decreased OS. Pcgf6 encodes the Pcgf6 protein, which interacts with some PcG proteins and serves as a transcription repressor . Previous studies have shown that Pcgf6 is a polycomb group protein that contains a ring finger motif and is a defining component of different PCR1‐type complexes .…”

Section: Discussionmentioning

confidence: 99%

Analysis of the clinicopathological characteristics, genetic phenotypes, and prognostic of pure mucinous adenocarcinoma

Chen

et al. 2019

Cancer Medicine

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Background: Primary pure mucinous adenocarcinoma of the lung (PMA) is a rare subtype. However, correlations between clinicopathological features and genetic phenotypes with survival have not been described comprehensively. Methods: Pure mucinous adenocarcinoma patient information collected from the Surveillance, Epidemiology, and End Results (SEER) database, the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University (FDZSH), and the Cancer Genome Atlas (TCGA) were extracted, evaluated, and compared with other lung adenocarcinomas (LUAD) patient data. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the functional importance of underlying molecular changes. Overall survival (OS) was evaluated with the Kaplan-Meier method. Univariate and multivariate analysis through Cox proportional hazard regression identified risk factors that predicted OS, and the results were used to construct a nomogram to predict OS for PMA patients. Results: Overall, 3622 patients, 41 patients, and 15 patients with PMA were identified from the SEER, FDZSH, and TCGA databases, respectively. There were 345 differentially expressed genes, 30 differentially mutated genes and 72 differentially methylated genes were identified between PMA and other LUAD samples. In the SEER database, PMA had a better prognosis compared to other LUAD. Compared with patients with other LUAD, patients with PMA exhibited unique clinicopathological features, including fewer grade III/IV tumors, less pleural invasion, more early-stage cancer, and more lower lobe carcinomas. Multivariate analyses showed that age, race, T stage, N stage, surgery, and chemotherapy were independent risk factors. The nomogram had a calibration index of 0.724. Conclusions: Our research identified unique clinicopathological characteristics and genetic phenotypes for PMA and other LUAD. The nomogram accurately predicted OS. K E Y W O R D S clinicopathological features, genetic analysis, nomogram, pure mucinous adenocarcinoma, the surveillance, epidemiology, and end results 518 | CHEN Et al. How to cite this article: Chen Z, Li M, Ma K, et al. Analysis of the clinicopathological characteristics, genetic phenotypes, and prognostic of pure mucinous adenocarcinoma. Cancer Med. 2020;9:517-529. https ://

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“…T cell-specific deletion of Ring1 and Ring2 converts T cell precursors to B cells (38,39). Silencing of PCGF6 enhances dendritic cell activation, suggesting a role for PRC1 in inflammatory processes (40). The vasculitis phenotype of the patient may reflect dysregulation of the immune system induced by disruption of RING1 activity.…”

Section: Discussionmentioning

confidence: 99%

De novo mutation in RING1 with epigenetic effects on neurodevelopment

Pierce

Stewart

Gülsüner

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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RING1 is an E3-ubiquitin ligase that is involved in epigenetic control of transcription during development. It is a component of the polycomb repressive complex 1, and its role in that complex is to ubiquitylate histone H2A. In a 13-year-old girl with syndromic neurodevelopmental disabilities, we identified a de novo mutation, RING1 p.R95Q, which alters a conserved arginine residue in the catalytic RING domain. In vitro assays demonstrated that the mutant RING1 retains capacity to catalyze ubiquitin chain formation, but is defective in its ability to ubiquitylate histone H2A in nucleosomes. Consistent with this in vitro effect, cells of the patient showed decreased monoubiquitylation of histone H2A. We modeled the mutant RING1 in by editing the comparable amino acid change into, the suggested ortholog. Animals with either the missense mutation or complete knockout of were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance. Relevant to our patient, animals heterozygous for either the missense or knockout allele also showed neuronal defects. Our results support three conclusions: mutation of is the likely cause of a human neurodevelopmental syndrome, mutation of can disrupt histone H2A ubiquitylation without disrupting RING1 catalytic activity, and the comparable mutation in both recapitulates the effects on histone H2A ubiquitylation and leads to neurodevelopmental abnormalities. This role for adds to our understanding of the importance of aberrant epigenetic effects as causes of human neurodevelopmental disorders.

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The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence

Cited by 34 publications

References 36 publications

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

Analysis of the clinicopathological characteristics, genetic phenotypes, and prognostic of pure mucinous adenocarcinoma

De novo mutation in RING1 with epigenetic effects on neurodevelopment

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