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Abstract
Objective: Histone modifications set transcriptional competency and can perpetuate pathologic expression patterns. We defined systemic lupus erythematosus (SLE)-specific changes in H3K4me3 and K3K27me3, histone marks of gene activation and repression, respectively. Methods: We used ChIP-seq to define histone modifications in monocytes from SLE patients and controls. Results: Both promoters and enhancers exhibited significant changes in histone methylation in SLE. Regions with differential H3K4me3 in SLE were significantly enriched in potential interferon-related transcription factor binding sites and pioneer transcription factor sites. Conclusion: Enhancer activation defines the character of the cell and our data support extensive disease effects in monocytes, a particularly plastic lineage. Type I interferons not only drive altered gene expression but may also alter the character of the cell through chromatin modifications.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/3dp-2022-0019
Acknowledgements
The authors gratefully acknowledge the contributions of patients, nurses and physicians and thank Eric Rappaport, Stephen Mahoney and Kristen Hunter from the nucleic acid core facility at CHOP for SOLiD sample preparation as well as Juan Perin for alignments.
Financial & competing interests disclosure
This study was supported in part by the Wallace Chair of Pediatrics, and NIH grants R01 ES017627 and AR43727. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.