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Int J Clin Rheumtol. 2011 Aug;6(4):423-439.

Epigenetics in systemic lupus erythematosus: leading the way for specific therapeutic agents.

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  • 1Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder of an unclearly determined etiology. Past studies, both epidemiological and biological, have implicated epigenetic influences in disease etiology and pathogenesis. Epigenetics describes changes in gene expression not linked to alterations in the underlying genomic sequence, and is most often typified by three modifications: methylation of DNA, addition of various side chains to histone groups and transcriptional regulation via short ncRNA sequences. The purpose of this article is to review the most important advances that link epigenetic changes to lupus. The contribution of DNA methylation changes to lupus pathogenesis is discussed. These include the role of apoptotic DNA, ultraviolet radiation, endogenous retroviruses, dietary contributions and aging. Hypomethylation of specific genes overexpressed in lupus T cells such as ITGAL (CD11a), CD40LG (CD40L), TNFSF7 (CD70), KIR2DL4 and PRF1 (perforin), and CD5 in lupus B cells seem to play an important role. Moreover, histone modifications such as increased global H4 acetylation in monocytes are highly associated with SLE. NcRNAs, especially miR-21, miR-148a and miR-126, control other elements of epigenetic regulation; particularly, transcription of the maintenance DNA methylation enzyme DNMT1. Epigenetic contributions to SLE etiology have been well established, but much is still unknown. Epigenome-wide studies coupled with functional analysis of the epigenomic changes discovered will uncover novel pathways important in disease pathogenesis. Epigenetic therapies for SLE may be feasible in the future, particularly if they are designed to target specific regions within the genome.

PMID:
22184503
[PubMed]
PMCID:
PMC3241218
Free PMC Article

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