New advances of DNA methylation and histone modifications in rheumatoid arthritis, with special emphasis on MeCP2.

Epigenetics is a steadily growing research area in many human diseases, especially in autoimmune diseases such as rheumatoid arthritis (RA). RA is an autoimmune disease with unclear etiology characterized by chronic inflammation and joint destruction and fibroblast-like synoviocytes (FLS) display a crucial role in the pathogenesis of RA. Even though the etiology is not yet fully understood, RA is generally considered to be caused by a combination of epigenetic modification, deregulated immunomodulation, and environmental factors. Epigenetic modifications, including DNA methylation and post-translational histone modifications, such as histone methylation and histone (de)acetylation are identified as regulatory mechanisms in controlling aggressive FLS activation in patients and animal models. In the last 3years, the field of epigenetics in RA has impressively increased. Methyl-CpG-binding protein 2 (MeCP2) is first identified as a transcriptional repressor that inhibits gene expression through the interpretation of two epigenetic markers, DNA methylation and histone modification. The cooperative action among MeCP2, DNA methylation and histone modifications indicates that MeCP2 should participate in the pathogenesis of RA through silence of certain gene transcription. In this review, we consider the role of DNA methylation and histone modifications in the development of RA, with a special focus on increased MeCP2 expression in RA animal models.