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Epigenomics. 2015;7(6):921-35. doi: 10.2217/epi.15.47. Epub 2015 Oct 7.

Monocyte enhancers are highly altered in systemic lupus erythematosus.

Author information

1
Division of Allergy & Immunology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
2
The Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA 1910, USA.
3
Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

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.

KEYWORDS:

IRF1; enhancer; epigenome; histone methylation; interferon; lupus

PMID:
26442457
PMCID:
PMC4864065
DOI:
10.2217/epi.15.47
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

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.

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