New advances of DNA methylation in liver fibrosis, with special emphasis on the crosstalk between microRNAs and DNA methylation machinery.

ABSTRACT

Epigenetics refers to the study of heritable changes in the pattern of gene expression that is controlled by a mechanism specifically not due to changes the primary DNA sequence. Well-known epigenetic mechanisms include DNA methylation, post-translational histone modifications and RNA-based mechanisms including those controlled by small non-coding RNAs (miRNAs). Recent studies have shown that epigenetic modifications orchestrate the hepatic stellate cell (HSC) activation and liver fibrosis. In this review we focus on the aberrant methylation of CpG island promoters of select genes is the prominent epigenetic mechanism to effectively silence gene transcription facilitating HSC activation and liver fibrosis. Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation and the interaction of DNA methylation with miRNAs involved in the regulation of HSC activation and liver fibrosis. Recent advances in epigenetics alterations in the pathogenesis of liver fibrosis and their possible use as new therapeutic targets and biomarkers.