Similar Datasets
Project description:Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
| S-EPMC5953939 | biostudies-literature
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112657 | GEO
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112655 | GEO
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112656 | GEO
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112654 | GEO
Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes
| PRJNA448630 | ENA
Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [WGBS]
| PRJNA448633 | ENA
Project description:ObjectiveSince previous studies indicate that metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), we undertook this study to determine if changes in the genome-wide chromatin and DNA states in genes associated with nutrient transporters could help to identify activated metabolic pathways in RA FLS.MethodsData from a previous comprehensive epigenomic study in FLS were analyzed to identify differences in genome-wide states and gene transcription between RA and osteoarthritis. We utilized the single nearest genes to regions of interest for pathway analyses. Homer promoter analysis was used to identify enriched motifs for transcription factors. The role of solute carrier transporters and glutamine metabolism dependence in RA FLS was determined by small interfacing RNA knockdown, functional assays, and incubation with CB-839, a glutaminase inhibitor. We performed 1 H nuclear magnetic resonance to quantify metabolites.ResultsThe unbiased pathway analysis demonstrated that solute carrier-mediated transmembrane transport was one pathway associated with differences in at least 4 genome-wide states or gene transcription. Thirty-four transporters of amino acids and other nutrients were associated with a change in at least 4 epigenetic marks. Functional assays revealed that solute carrier family 4 member 4 (SLC4A4) was critical for invasion, and glutamine was sufficient as an alternate source of energy to glucose. Experiments with CB-839 demonstrated decreased RA FLS invasion and proliferation. Finally, we found enrichment of motifs for c-Myc in several nutrient transporters.ConclusionOur findings demonstrate that changes in the epigenetic landscape of genes are related to nutrient transporters, and metabolic pathways can be used to identify RA-specific targets, including critical solute carrier transporters, enzymes, and transcription factors, to develop novel therapeutic agents.
| S-EPMC9246826 | biostudies-literature
Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [RNA-seq]
| PRJNA448634 | ENA
Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [ATAC-seq]
| PRJNA448631 | ENA