title: A new epigenetic challenge: systemic lupus erythematosus.
abstract: In recent years, compelling evidence has been gathered that supports a role for epigenetic alterations in the pathogenesis of systemic lupus erythematosus (SLE). Different blood cell populations of SLE patients are characterized by a global loss of DNA methylation. This process is associated with defects in ERK pathway signalling and consequent DNMT 1 downregulation. Hypomethylation of gene promoters has been described, which permits transcriptional activation and therefore functional changes in the cells and also hypomethylation of the ribosomal RNA gene cluster. Among the identified targets undergoing demethylation are genes involved in autoreactivity (ITGAL), osmotic lysis and apoptosis (PRF1, MMP14 and LCN2), antigen presentation (CSF3R), inflammation(MMP 14), B- T-cell interaction (CD70 and CD40LG) and cytokine pathways (CSF3R, IL-4, IL-6 and IFNGR2). DNA methylation inhibitors are also known to induce autoreactivity in vitro and cause a lupus-like disease in vivo. Further, altered patterns of histone modifications have been described in SLE. CD4+ lymphocytes undergo global histone H3 and H4 deacetylation and consequent skewed gene expression. Although multiple lines of evidence highlight the contribution of epigenetic alterations to the pathogenesis of lupus in genetically predisposed individuals, many questions remain to be answered. Attaining a deeper understanding of these matters will create opportunities in the promising area of epigenetic treatments.
authors.affiliation: Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Biola M
authors.initials: BM
authors.lastname: Javierre
authors.forename: Bruce
authors.initials: B
authors.lastname: Richardson
mesh_terms: D000818:Animals; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*
chemical_list: D006657:Histones