Critical Link Between Epigenetics and Transcription Factors in the Induction of Autoimmunity: a Comprehensive Review

Haijing Wu, Ming Zhao, Akihiko Yoshimura, Christopher Chang, Qianjin Lu

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Autoimmune diseases occur when the immune system loses tolerance to self-antigens, inducing inflammation and tissue damage. The pathogenesis of autoimmune diseases has not been elucidated. A growing mountain of evidence suggests the involvement of genetic and epigenetic factors in the development of these disorders. Genetic mapping has identified several candidate variants in autoimmune conditions. However, autoimmune diseases cannot be explained by genetic susceptibility alone. The fact that there is only 20 % of concordance for systemic lupus erythematosus (SLE) in homozygotic twins is an indication that epigenetics and environment may also play significant roles. Epigenetics refer to inheritable and potentially reversible changes in DNA and chromatin that regulate gene expression without altering the DNA sequence. The primary mechanisms of epigenetic regulation include DNA methylation, histone modification, and non-coding RNA-mediated regulation. The regulation on gene expression by epigenetics is similar to that by transcription factors (TFs), and the normal execution of biological event is controlled by a combination of epigenetic modifications and TFs. These two mechanisms share similar regulatory logistics and cooperate in part by influencing activity of the binding sites of target genes. In addition, the promoters of TFs have been found themselves to be modified by epigenetic regulators and TFs can also induce epigenetic changes. There is a two-way street in which interplay between epigenetic regulation and TFs plays a role in the pathogenesis of SLE, rheumatoid arthritis, type 1 diabetes, systemic sclerosis, and multiple sclerosis. Understanding of pathogenesis of these autoimmune diseases will help define potential targets for therapeutic strategies.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalClinical Reviews in Allergy and Immunology
DOIs
Publication statusAccepted/In press - 2016 Mar 11

Keywords

  • Autoimmune
  • DNA methylation
  • Epigenetics
  • Histone modifications
  • lncRNAs
  • miRNAs
  • Transcription factors

ASJC Scopus subject areas

  • Immunology and Allergy

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