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Epigenetic analysis in rheumatoid arthritis synoviocytes.

ABSTRACT: Rheumatoid arthritis (RA) is a complex chronic systematic disease with progressive destruction of the joints by invasive synoviocytes. To characterize the key regulators involved in the development of RA, we obtained multilayer epigenomics data including DNA methylation by whole-genome bisulfite sequencing, miRNA profiles, genetic variations by whole-exome sequencing, and mRNA profiles from synoviocytes of RA and osteoarthritis (OA) patients. The overall DNA methylation patterns were not much different between RA and OA, but 523 low-methylated regions (LMRs) were specific to RA. The LMRs were preferentially localized at the 5' introns and overlapped with transcription factor binding motifs for GLI1, RUNX2, and TFAP2A/C. Single base-scale differentially methylated CpGs were linked with several networks related to wound response, tissue development, collagen fibril organization, and the TGF-? receptor signaling pathway. Further, the DNA methylation of 201 CpGs was significantly correlated with 27 expressed miRNA genes. Our interpretation of epigenomic data of the synoviocytes from RA and OA patients is an informative resource to further investigate regulatory elements and biomarkers responsible for the pathophysiology of RA and OA.

SUBMITTER: Ham S

PROVIDER: S-EPMC6395697 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.

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.

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Epigenetic Regulation of Nutrient Transporters in Rheumatoid Arthritis Fibroblast-like Synoviocytes.

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| S-EPMC9246826 | biostudies-literature

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-04-30 | GSE112658 | GEO

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [WGBS]

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

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [RNA-seq]

2018-04-30 | GSE112656 | GEO

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [ChIP-seq]

2018-04-30 | GSE112655 | GEO

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [ATAC-seq]

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Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes.

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Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes

Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes

| PRJNA448630 | ENA

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

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| S-EPMC5328845 | biostudies-literature

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