Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes

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 Nagpal, Kurtis E. Bachman, Richard I. Ainsworth, Mengchi Wang, Bo Ding, Percio S. Gulko (), Wei Wang () and Gary S. Firestein ()
Additional contact information
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
Gary S. Firestein: Division of Rheumatology, Allergy and Immunology

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04310-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04310-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04310-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().