β-Arrestin1/miR-326 Transcription Unit Is Epigenetically Regulated in Neural Stem Cells Where It Controls Stemness and Growth Arrest

Figure 7

miR-326 and β-arrestin1 are epigenetically silenced and control stemness features in cerebellar NSCs. We propose a model in which epigenetic silencing of the intragenic miR-326 and its host gene, β-arrestin1, maintains physiological neuronal stemness. In cerebellar NSCs miR-326 and β-arrestin1 are epigenetically silenced through hypermethylation of CpG islands on their common promoter, leading to a permissive molecular environment for the expression of prostemness and proproliferative cues. Upon differentiation or demethylating treatment, the promoter of the locus miR-326/β-arrestin1 is demethylated and thus the expression levels of miR-326 and β-arrestin1 are upregulated. While miR-326 targets molecules belonging to the Hedgehog pathway and the Notch pathway, thus hampering stemness properties, β-arrestin1 acts as a cofactor for the transcriptional activation of p27, leading to cell cycle arrest.