An epigenetic feedback regulatory loop involving microRNA-195 and MBD1 governs neural stem cell differentiation.

ABSTRACT:

Background

Epigenetic mechanisms, including DNA methylation, histone modification, and microRNAs, play pivotal roles in stem cell biology. Methyl-CpG binding protein 1 (MBD1), an important epigenetic regulator of adult neurogenesis, controls the proliferation and differentiation of adult neural stem/progenitor cells (aNSCs). We recently demonstrated that MBD1 deficiency in aNSCs leads to altered expression of several noncoding microRNAs (miRNAs).

Methodology/principal findings

Here we show that one of these miRNAs, miR-195, and MBD1 form a negative feedback loop. While MBD1 directly represses the expression of miR-195 in aNSCs, high levels of miR-195 in turn repress the expression of MBD1. Both gain-of-function and loss-of-function investigations show that alterations of the MBD1-miR-195 feedback loop tip the balance between aNSC proliferation and differentiation.

Conclusions/significance

Therefore the regulatory loop formed by MBD1 and miR-195 is an important component of the epigenetic network that controls aNSC fate.

SUBMITTER: Liu C 

PROVIDER: S-EPMC3547917 | biostudies-literature |

REPOSITORIES: biostudies-literature