Histone modifications underlie monocyte dysregulation in patients with systemic sclerosis, underlining the treatment potential of epigenetic targeting

Annals of the Rheumatic Diseases
Maarten van der KroefMarzia Rossato

Abstract

Systemic sclerosis (SSc) is a severe autoimmune disease, in which the pathogenesis is dependent on both genetic and epigenetic factors. Altered gene expression in SSc monocytes, particularly of interferon (IFN)-responsive genes, suggests their involvement in SSc development. We investigated the correlation between epigenetic histone marks and gene expression in SSc monocytes. Chromatin immunoprecipitation followed by sequencing (ChIPseq) for histone marks H3K4me3 and H3K27ac was performed on monocytes of nine healthy controls and 14 patients with SSc. RNA sequencing was performed in parallel to identify aberrantly expressed genes and their correlation with the levels of H3K4me3 and H3K27ac located nearby their transcription start sites. ChIP-qPCR assays were used to verify the role of bromodomain proteins, H3K27ac and STATs on IFN-responsive gene expression. 1046 and 534 genomic loci showed aberrant H3K4me3 and H3K27ac marks, respectively, in SSc monocytes. The expression of 381 genes was directly and significantly proportional to the levels of such chromatin marks present near their transcription start site. Genes correlated to altered histone marks were enriched for immune, IFN and antiviral pathways and presented with recurr...Continue Reading

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Citations

Mar 5, 2020·Expert Review of Clinical Immunology·Desiré Casares-MarfilMarialbert Acosta-Herrera
May 28, 2019·Current Rheumatology Reports·Diana M Toledo, Patricia A Pioli
Jul 16, 2019·Current Rheumatology Reports·Marialbert Acosta-HerreraJavier Martín
Dec 10, 2019·Current Rheumatology Reports·Pei-Suen Tsou
Jun 12, 2020·Therapeutic Advances in Musculoskeletal Disease·Bianca Saveria FiorettoMarco Matucci-Cerinic
Feb 26, 2019·Frontiers in Immunology·Barbara MariottiFlavia Bazzoni
Apr 3, 2019·Arthritis & Rheumatology·Weiyang TaoAridaman Pandit
Jan 20, 2021·Signal Transduction and Targeted Therapy·Nian WangRui Kang
Sep 5, 2021·Nature Reviews. Rheumatology·Pei-Suen TsouSteven O'Reilly

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