6533b871fe1ef96bd12d270e
RESEARCH PRODUCT
TET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn.
Mitsuteru ItoWolf ReikWolf ReikSacri R. FerrónChristel KruegerAnna Lozano-ureñaRaquel Montalbán-loroAnne C. Ferguson-smithsubject
0301 basic medicineScienceCellular differentiationGeneral Physics and AstronomySubventricular zone02 engineering and technologyBiologyDNA-binding proteinArticleGeneral Biochemistry Genetics and Molecular BiologyCatalysissnRNP Core ProteinsDioxygenases03 medical and health sciencesMiceNeural Stem CellsLateral VentriclesProto-Oncogene ProteinsmedicineAnimalsRNA Small Interferinglcsh:SciencePsychological repressionreproductive and urinary physiologyMultidisciplinarySnRNP Core ProteinsQNeurogenesisBrainCell DifferentiationGeneral Chemistry021001 nanoscience & nanotechnologyNeural stem cellnervous system diseasesCell biologyDNA-Binding Proteins030104 developmental biologymedicine.anatomical_structurenervous systemAstrocyteslcsh:Qbiological phenomena cell phenomena and immunity0210 nano-technologyGenomic imprintingSignal Transductiondescription
Ten-eleven-translocation (TET) proteins catalyze DNA hydroxylation, playing an important role in demethylation of DNA in mammals. Remarkably, although hydroxymethylation levels are high in the mouse brain, the potential role of TET proteins in adult neurogenesis is unknown. We show here that a non-catalytic action of TET3 is essentially required for the maintenance of the neural stem cell (NSC) pool in the adult subventricular zone (SVZ) niche by preventing premature differentiation of NSCs into non-neurogenic astrocytes. This occurs through direct binding of TET3 to the paternal transcribed allele of the imprinted gene Small nuclear ribonucleoprotein-associated polypeptide N (Snrpn), contributing to transcriptional repression of the gene. The study also identifies BMP2 as an effector of the astrocytic terminal differentiation mediated by SNRPN. Our work describes a novel mechanism of control of an imprinted gene in the regulation of adult neurogenesis through an unconventional role of TET3.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-04-12 |