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Global H4 acetylation analysis by ChIP-chip in systemic lupus erythematosus monocytes

Abstract

Systemic lupus erythematosus (SLE) is a polygenic disorder affecting approximately 1 in 1000 adults. Recent data have implicated interferons (IFN) in the pathogenesis, and the expressions of many genes downstream of IFNs are regulated at the level of histone modifications. We examined H4 acetylation (H4ac) and gene expression in monocytes from patients with SLE to define alterations to the epigenome. Monocytes from 14 controls and 24 SLE patients were used for analysis by chromatin immunoprecipitation for H4ac and gene expression arrays. Primary monocytes treated with α-IFN were used as a comparator. Data were analyzed for concordance of H4ac and gene expression. Network analyses and transcription factor analyses were conducted to identify potential pathways. H4ac was significantly altered in monocytes from patients with SLE. In all, 63% of genes with increased H4ac had the potential for regulation by IFN regulatory factor (IRF)1. IRF1 binding sites were also upstream of nearly all genes with both increased H4ac and gene expression. α-IFN was a significant contributor to both expression and H4ac patterns, but the greatest concordance was seen in the enrichment of certain transcription factor binding sites upstream of genes with increased H4ac in SLE and genes with increased H4ac after α-IFN treatment.

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Acknowledgements

We thank Jason Rhodes for collating the clinical data on patients and Juan Perin for MAT analyses. We also acknowledge Eric Rappaport and Virginia Kocieda for early assay development. This work was supported by 1RO1 AI 51323-01. The Hopkins Lupus Cohort is supported by NIH AR 43727 and by the Johns Hopkins University School of Medicine Outpatient General Clinical Research Center M01-RR00052.

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Correspondence to K E Sullivan.

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Zhang, Z., Song, L., Maurer, K. et al. Global H4 acetylation analysis by ChIP-chip in systemic lupus erythematosus monocytes. Genes Immun 11, 124–133 (2010). https://doi.org/10.1038/gene.2009.66

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