Center for Biomedical Informatics, Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA.
Genes Immun. 2010 Mar;11(2):124-33. doi: 10.1038/gene.2009.66. Epub 2009 Aug 27.
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 alpha-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. alpha-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 alpha-IFN treatment.
系统性红斑狼疮 (SLE) 是一种影响约千分之一成年人的多基因疾病。最近的数据表明干扰素 (IFN) 在发病机制中起作用，IFNs 下游的许多基因的表达在组蛋白修饰水平上受到调节。我们研究了 SLE 患者单核细胞中的 H4 乙酰化 (H4ac) 和基因表达，以定义表观基因组的改变。使用染色质免疫沉淀法检测了来自 14 名对照和 24 名 SLE 患者的单核细胞中的 H4ac 和基因表达谱。用 α-IFN 处理的原代单核细胞作为比较。分析了 H4ac 和基因表达的一致性。进行了网络分析和转录因子分析，以确定潜在的途径。SLE 患者单核细胞中的 H4ac 明显改变。总的来说，具有增加的 H4ac 的基因中有 63% 具有被干扰素调节因子 (IRF)1 调节的潜力。IRF1 结合位点也位于几乎所有具有增加的 H4ac 和基因表达的基因的上游。α-IFN 是表达和 H4ac 模式的重要贡献者，但在 SLE 中具有增加的 H4ac 的基因和 α-IFN 处理后具有增加的 H4ac 的基因的某些转录因子结合位点的富集方面，一致性最大。
