Towards an understanding of the role of DNA methylation in rheumatoid arthritis: therapeutic and diagnostic implications

Abstract

The term 'epigenetics' loosely describes DNA-templated processes leading to heritable changes in gene activity and expression, which are independent of the underlying DNA sequence. Epigenetic mechanisms comprise of post-translational modifications of chromatin, methylation of DNA, nucleosome positioning as well as expression of noncoding RNAs. Major advances in understanding the role of DNA methylation in regulating chromatin functions have been made over the past decade, and point to a role of this epigenetic mechanism in human disease. Rheumatoid arthritis (RA) is an autoimmune disorder where altered DNA methylation patterns have been identified in a number of different disease-relevant cell types. However, the contribution of DNA methylation changes to RA disease pathogenesis is at present poorly understood and in need of further investigation. Here we review the current knowledge regarding the role of DNA methylation in rheumatoid arthritis and indicate its potential therapeutic implications.

Epigenetics in rheumatoid arthritis; fibroblast‐like synoviocytes as an emerging paradigm in the pathogenesis of the disease

“…There are three DNMTs in mammalian cells: DNMT1 is responsible for maintaining the existing DNA methylation pattern, whereas DNMT3a and 3b are responsible for de novo methylation . Despite the previous theory, in which the DNA cytosine methylation was regarded as a stable epigenetic mark, recent studies have documented that this phenomenon is not as static as previously thought . Changes in the environment, such as variation in the amount of methyl donors in diet, could change the DNA methylation; hence, it could be considered as a dynamic process .…”

“…35 Despite the previous theory, in which the DNA cytosine methylation was regarded as a stable epigenetic mark, recent studies have documented that this phenomenon is not as static as previously thought. 36 Changes in the environment, such as variation in the amount of methyl donors in diet, could change the DNA methylation; hence, it could be considered as a dynamic process. 17 DNA demethylation can be induced by either active or passive mechanism.…”

Cell-type-specific resolution epigenetics without the need for cell sorting or single-cell biology

“…RA is an autoimmune chronic inflammatory disease which has been previously related to changes in DNA methylation 31,32 . In order to further demonstrate the utility of TCA, we revisited the largest previous whole-blood methylation study with RA by Liu et al ( n = 658) 19 .…”

Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling

“…Thus, regardless of the initiating insult, myofibroblasts share common markers like the fibroblast-activation protein and α-smooth muscle protein and, importantly, maintain a stable phenotype when severed from the cellular source of their generation (12,13). This phenotypic durability relies on the reprogramming of their epigenetic landscape (11,(14)(15)(16)(17), a well attested genomic signature in CAFs (18)(19)(20)(21).…”