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The underlying pathogenesis of many TCD remains unknown until now, but recently, studies have demonstrated that epigenetic modifications might induce and/or accelerate the development of auto-immunity. These modifications include alteration of DNA methylation, chromatin remodeling, and micro-RNAs, which are the main focus of this book, in which we discuss the involvement of epigenetics in two of the Connective tissue diseases: Rheumatoid arthritis (RA) and Systemic lupus erythematosus (SLE).