Journal
EPIGENOMICS
Volume 7, Issue 6, Pages 921-935Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi.15.47
Keywords
enhancer; epigenome; histone methylation; interferon; IRF1; lupus
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Funding
- Wallace Chair of Pediatrics
- NIH [R01 ES017627, AR43727]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR043727] Funding Source: NIH RePORTER
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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.
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