PT  - JOURNAL ARTICLE
AU  - Sara Zocher
AU  - Rupert W Overall
AU  - Gabriel Berdugo-Vega
AU  - Nicole Rund
AU  - Anne Karasinsky
AU  - Vijay S Adusumilli
AU  - Christina Steinhauer
AU  - Sina Scheibenstock
AU  - Kristian Händler
AU  - Joachim L Schultze
AU  - Federico Calegari
AU  - Gerd Kempermann
TI  - <em>De novo</em> DNA methylation controls neuronal maturation during adult hippocampal neurogenesis
AID  - 10.1101/2020.09.22.308692
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.22.308692
4099  - http://biorxiv.org/content/early/2020/09/22/2020.09.22.308692.short
4100  - http://biorxiv.org/content/early/2020/09/22/2020.09.22.308692.full
AB  - Dynamic DNA methylation controls gene-regulatory networks underlying cell fate specification. How DNA methylation patterns change during adult hippocampal neurogenesis and their relevance for adult neural stem cell differentiation and related brain function has, however, remained unknown. Here, we show that neurogenesis-associated de novo DNA methylation is critical for maturation and functional integration of adult-born hippocampal neurons. Cell stage-specific bisulfite sequencing revealed a pronounced gain of DNA methylation at neuronal enhancers, gene bodies and binding sites of pro-neuronal transcription factors during adult neurogenesis, which mostly correlated with transcriptional up-regulation of the associated loci. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells specifically impaired dendritic outgrowth and synaptogenesis of new-born neurons, resulting in reduced hippocampal excitability and specific deficits in hippocampus-dependent learning and memory. Our results highlight that, during adult neurogenesis, remodeling of neuronal methylomes is fundamental for proper hippocampal function.Competing Interest StatementThe authors have declared no competing interest.