Cytokine-induced monocyte characteristics in SLE.
Monocytes in SLE have been described as having aberrant behavior in a number of assays. We examined gene expression and used a genome-wide approach to study the posttranslational histone mark, H4 acetylation, to examine epigenetic changes in SLE monocytes. We compared SLE monocyte gene expression and H4 acetylation with three types of cytokine-treated monocytes to understand which cytokine effects predominated in SLE monocytes. We found that gamma-interferon and alpha-interferon both replicated a broad range of the gene expression changes seen in SLE monocytes. H4 acetylation in SLE monocytes was overall higher than in controls and there was less correlation of H4ac with cytokine-treated cells than when gene expression was compared. A set of chemokine genes had downregulated expression and H4ac. Therefore, there are significant clusters of aberrantly expressed genes in SLE which are strongly associated with altered H4ac, suggesting that these cells have experienced durable changes to their epigenome.
Zhang
Zhe
Z
The Center for Bioinformatics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Maurer
Kelly
K
Perin
Juan C
JC
Song
Li
L
Sullivan
Kathleen E
KE
D000107:Acetylation / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016000:Cluster Analysis; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics
D015415:Biomarkers; D016207:Cytokines; D006657:Histones; D007372:Interferons