<i>De novo</i>DNA methylation controls neuronal maturation during adult hippocampal neurogenesis
Summary 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-associatedde novoDNA 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 bothde novoDNA methyltransferasesDnmt3aandDnmt3bin 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..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 20. Nov. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zocher, Sara [VerfasserIn] |
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| doi: |
10.1101/2020.09.22.308692 |
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| PPN (Katalog-ID): |
XBI018807615 |
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| 245 | 1 | 0 | |a <i>De novo</i>DNA methylation controls neuronal maturation during adult hippocampal neurogenesis |
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| 520 | |a Summary 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-associatedde novoDNA 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 bothde novoDNA methyltransferasesDnmt3aandDnmt3bin 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. | ||
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| 700 | 1 | |a Overall, Rupert W |e verfasserin |4 aut | |
| 700 | 1 | |a Berdugo-Vega, Gabriel |e verfasserin |4 aut | |
| 700 | 1 | |a Rund, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Karasinsky, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Adusumilli, Vijay S |e verfasserin |4 aut | |
| 700 | 1 | |a Steinhauer, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Scheibenstock, Sina |e verfasserin |4 aut | |
| 700 | 1 | |a Händler, Kristian |e verfasserin |4 aut | |
| 700 | 1 | |a Schultze, Joachim L |e verfasserin |4 aut | |
| 700 | 1 | |a Calegari, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Kempermann, Gerd |e verfasserin |4 aut | |
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