The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Cell Stem Cell. 2013 Aug 1;13(2):237-45. doi: 10.1016/j.stem.2013.05.006. Epub 2013 Jun 13.
DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in embryonic stem cells and neurons in mammals. However, its biological function in vivo is largely unknown. Here, we demonstrate that Tet1 plays an important role in regulating neural progenitor cell proliferation in adult mouse brain. Mice lacking Tet1 exhibit impaired hippocampal neurogenesis accompanied by poor learning and memory. In adult neural progenitor cells deficient in Tet1, a cohort of genes involved in progenitor proliferation were hypermethylated and downregulated. Our results indicate that Tet1 is positively involved in the epigenetic regulation of neural progenitor cell proliferation in the adult brain.
Tet 双加氧酶催化的 DNA 羟化在哺乳动物的胚胎干细胞和神经元中大量发生。然而,其在体内的生物学功能在很大程度上仍是未知的。在这里,我们证明 Tet1 在调节成年小鼠大脑中的神经祖细胞增殖方面起着重要作用。缺乏 Tet1 的小鼠表现出海马神经发生受损,伴有学习和记忆能力差。在缺乏 Tet1 的成年神经祖细胞中,一组参与祖细胞增殖的基因被超甲基化和下调。我们的结果表明,Tet1 积极参与成年大脑中神经祖细胞增殖的表观遗传调控。