Cross talk between microRNA and epigenetic regulation in adult neurogenesis

Abstract

The microRNA miR-137 represses expression of Ezh2, a histone methyltransferase, which in turn alters the epigenetic architecture of chromatin that is important for regulation of miR-137 levels.

Abstract

Both microRNAs (miRNAs) and epigenetic regulation have important functions in stem cell biology, although the interactions between these two pathways are not well understood. Here, we show that MeCP2, a DNA methyl-CpG–binding protein, can epigenetically regulate specific miRNAs in adult neural stem cells (aNSCs). MeCP2-mediated epigenetic regulation of one such miRNA, miR-137, involves coregulation by Sox2, a core transcription factor in stem cells. miR-137 modulates the proliferation and differentiation of aNSCs in vitro and in vivo. Overexpression of miR-137 promotes the proliferation of aNSCs, whereas a reduction of miR-137 enhances aNSC differentiation. We further show that miR-137 post-transcriptionally represses the expression of Ezh2, a histone methyltransferase and Polycomb group (PcG) protein. The miR-137–mediated repression of Ezh2 feeds back to chromatin, resulting in a global decrease in histone H3 trimethyl lysine 27. Coexpression of Ezh2 can rescue phenotypes associated with miR-137 overexpression. These results demonstrate that cross talk between miRNA and epigenetic regulation contributes to the modulation of adult neurogenesis.