Global H4 acetylation analysis by ChIP-chip in SLE monocytes

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