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Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes

Author

Listed:
  • Rizi Ai

    (Department of Chemistry and Biochemistry)

  • Teresina Laragione

    (Icahn School of Medicine at Mount Sinai)

  • Deepa Hammaker

    (Division of Rheumatology, Allergy and Immunology)

  • David L. Boyle

    (Division of Rheumatology, Allergy and Immunology)

  • Andre Wildberg

    (Department of Chemistry and Biochemistry)

  • Keisuke Maeshima

    (Division of Rheumatology, Allergy and Immunology)

  • Emanuele Palescandolo

    (Janssen Pharmaceuticals)

  • Vinod Krishna

    (Janssen Pharmaceuticals)

  • David Pocalyko

    (Janssen Pharmaceuticals)

  • John W. Whitaker

    (Janssen Pharmaceuticals)

  • Yuchen Bai

    (Janssen Pharmaceuticals)

  • Sunil Nagpal

    (Janssen Pharmaceuticals)

  • Kurtis E. Bachman

    (Janssen Pharmaceuticals)

  • Richard I. Ainsworth

    (Department of Chemistry and Biochemistry)

  • Mengchi Wang

    (Department of Chemistry and Biochemistry)

  • Bo Ding

    (Department of Chemistry and Biochemistry)

  • Percio S. Gulko

    (Icahn School of Medicine at Mount Sinai)

  • Wei Wang

    (Department of Chemistry and Biochemistry
    Department of Cellular and Molecular Medicine)

  • Gary S. Firestein

    (Division of Rheumatology, Allergy and Immunology)

Abstract

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.

Suggested Citation

  • Rizi Ai & Teresina Laragione & Deepa Hammaker & David L. Boyle & Andre Wildberg & Keisuke Maeshima & Emanuele Palescandolo & Vinod Krishna & David Pocalyko & John W. Whitaker & Yuchen Bai & Sunil Nagp, 2018. "Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04310-9
    DOI: 10.1038/s41467-018-04310-9
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