Figure 4.

Epigenetic mechanisms and regulation of EndMT. Schematic representation of epigenetic modifications and ncRNA-mediated regulation of EndMT. HDAC3 recruits EZH2 that via H3K27me3 deposition silences TGF-β signalling and blocks EndMT. HDAC9 induces EndMT by repressing H3K9 and H3K27 acetylation. Histone demethylase JMJD2B advances EndMT by demethylating the repressive H3K9me3 at promoters of EndMT controlling genes. LncRNAs H19 and MALAT1 activate the EndMT transcriptional programme by activating the TGF-β and WNT/β-catenin cascades, respectively. LncRNAs GATA6-AS and MIR503HG act by inhibiting EndMT and maintaining EC identity. Many miRNAs have been implicated in regulating EndMT, by either inhibiting or promoting this process, either directly or indirectly. For example, dysregulation of FGF signalling results in reduced let-7 miRNA levels, which in turn increases TGF-β signalling and induces EndMT.