title: Cross talk between microRNA and epigenetic regulation in adult neurogenesis.
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.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Keith E
authors.initials: KE
authors.lastname: Szulwach
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smrt
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.forename: Yuping
authors.initials: Y
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Santistevan
authors.forename: Wendi
authors.initials: W
authors.lastname: Li
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
chemical_list: D002843:Chromatin; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2