title: Epigenetic regulation and the pathogenesis of systemic lupus erythematosus.
abstract: The pathogenesis of systemic lupus erythematosus (SLE) is incompletely understood. Studies in both lupus animal models and human disease indicate a clear role for epigenetic defects, particularly DNA methylation, in the pathogenesis of lupus. T-cell DNA from active lupus patients is hypomethylated, which results in overexpression of methylation-regulated genes, T-cell autoreactivity, and autoimmunity in vivo. Inducing an extracellular signal-regulated kinase (ERK) signaling defect in T cells using a transgenic mouse model resulted in reduced DNA methyltransferase 1 (DNMT1) expression, overexpression of methylation-sensitive genes, and anti-double-stranded DNA (anti-dsDNA) antibody production. ERK signaling is known to be defective in lupus T cells, and this defect is now explained by impaired T-cell protein kinase C (PKC) delta activation. Herein, we discuss how defective epigenetic regulation is involved in the pathogenesis of lupus, which includes both DNA methylation and histone modification changes.
authors.affiliation: Arthritis & Immunology Program, Oklahoma Medical Research Foundation, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Pan
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D000818:Animals; D041321:Chromosomes, Human, X; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006657:Histones; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2