Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition

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. •Tet1 knockout mice show poor learning and memory•Tet1 positively regulates adult hippocampal neural progenitor cell proliferation•Tet1 maintains target gene expression by protecting them from methylation•Tet1 deletion does not affect brain development Regulation of neural progenitor proliferation underlies defects in adult hippocampal neurogenesis in Tet1 null mice.