Fig. 1: DNA methylation, histone modifications, ATP-dependent chromatin remodeling, and miRNAs mediate epigenetic changes.

Chromatin is composed of proteins (histones) and DNA that form chromosomes, and the spatial organization of chromatin is critical for gene expression regulation. Epigenetic machinery, including methylation of DNA and histone modifications, directly orchestrates chromatin activity, mediating the balance between an inactive (heterochromatin) or an active form (euchromatin). DNA methylation occurs by adding a methyl group (-CH3) to cytosine. This process is catalyzed by enzymes such as the activity of DNA methyltransferases (DNMTs). Histone modification includes methylation (Me), acetylation (Ac), phosphorylation (P), ubiquitination (U), and citrullination (C) on N-terminal tails. ISWI, CHD, SWI/SNF, and INO80 are the major subfamilies of ATP-dependent chromatin remodelers. In contrast to above mentioned epigenetic modifications, miRNAs are not directly involved in chromatin activity; however, as potent posttranslational regulators of gene expression, miRNAs may regulate the expression of enzymes involved in direct modifications of chromatin, including DNMTs, ten-eleven translocation (TETs) methyl dioxygenases (involved in DNA demethylation), histone deacetylases (HDACs), and histone-lysine N-methyltransferase enzymes belonging to EZH family (enhancer of zest homolog). Created with BioRender.com.