ERI BiotecMed/Departamento de Biología Celular, Universidad de Valencia, 46100, Valencia, Spain.
Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
Nat Commun. 2019 Apr 12;10(1):1726. doi: 10.1038/s41467-019-09665-1.
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.
十号十一号易位（TET）蛋白催化 DNA 羟化，在哺乳动物的 DNA 去甲基化中发挥重要作用。值得注意的是，尽管小鼠大脑中的羟甲基化水平很高，但 TET 蛋白在成年神经发生中的潜在作用尚不清楚。我们在这里表明，TET3 的非催化作用对于维持成年侧脑室下区（SVZ）龛中的神经干细胞（NSC）库是必需的，通过防止 NSC 过早分化为非神经源性星形胶质细胞。这是通过 TET3 与印迹基因小核核糖核蛋白相关多肽 N（Snrpn）的父本转录等位基因的直接结合来实现的，有助于基因的转录抑制。该研究还确定了 BMP2 作为 SNRPN 介导的星形胶质细胞终末分化的效应因子。我们的工作描述了一种通过 TET3 的非传统作用，在调节成年神经发生中控制印迹基因的新机制。
