Journal Article

DZNE-2021-01519

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.

Zocher, S. (First author)DZNE* ; Overall, R.DZNE* ; Berdugo-Vega, G. ; Rund, N.DZNE* ; Karasinsky, A.DZNE* ; Adusumilli, V. S.DZNE* ; Steinhauer, C.DZNE* ; Scheibenstock, S.DZNE* ; Händler, K.DZNE* ; Schultze, J. L.DZNE* ; Calegari, F. ; Kempermann, G. (Last author)DZNE*

2021
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.15252/embj.2020107100

Abstract: Adult neurogenesis enables the life-long addition of functional neurons to the hippocampus and is regulated by both cell-intrinsic molecular programs and behavioral activity. De novo DNA methylation is crucial for embryonic brain development, but its role during adult hippocampal neurogenesis has remained unknown. Here, we show that de novo DNA methylation is critical for maturation and functional integration of adult-born neurons in the mouse hippocampus. Bisulfite sequencing revealed that de novo DNA methyltransferases target neuronal enhancers and gene bodies during adult hippocampal neural stem cell differentiation, to establish neuronal methylomes and facilitate transcriptional up-regulation of neuronal genes. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells did not affect proliferation or fate specification, but specifically impaired dendritic outgrowth and synaptogenesis of newborn neurons, thereby hampering their functional maturation. Consequently, abolishing de novo DNA methylation modulated activation patterns in the hippocampal circuitry and caused specific deficits in hippocampus-dependent learning and memory. Our results demonstrate that proper establishment of neuronal methylomes during adult neurogenesis is fundamental for hippocampal function.

Keyword(s): Animals (MeSH) ; Cell Differentiation: genetics (MeSH) ; Cells, Cultured (MeSH) ; DNA Methylation (MeSH) ; Epigenesis, Genetic (MeSH) ; Gene Expression Regulation (MeSH) ; Hippocampus: physiology (MeSH) ; Mice (MeSH) ; Neurogenesis: genetics (MeSH) ; Pyramidal Cells: cytology (MeSH) ; Pyramidal Cells: metabolism (MeSH) ; DNA methylation ; Dnmt3a ; adult neurogenesis ; hippocampus ; neuron maturation

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Contributing Institute(s):

1. Adult Neurogenesis (AG Kempermann)
2. Nuclear Architecture in Neural Plasticity and Aging (AG Toda)
3. Platform for Single Cell Genomics and Epigenomics (Schultze - PRECISE)
4. Platform for Single Cell Genomics and Epigenomics at DZNE & University of Bonn (R&D PRECISE)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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