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@ARTICLE{Zocher:162864,
author = {Zocher, Sara and Overall, Rupert and Berdugo-Vega, Gabriel
and Rund, Nicole and Karasinsky, Anne and Adusumilli, Vijay
S and Steinhauer, Christina and Scheibenstock, Sina and
Händler, Kristian and Schultze, Joachim L and Calegari,
Federico and Kempermann, Gerd},
title = {{D}e novo {DNA} methylation controls neuronal maturation
during adult hippocampal neurogenesis.},
journal = {The EMBO journal},
volume = {40},
number = {18},
issn = {1460-2075},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2021-01519},
pages = {e107100},
year = {2021},
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.},
keywords = {Animals / Cell Differentiation: genetics / Cells, Cultured
/ DNA Methylation / Epigenesis, Genetic / Gene Expression
Regulation / Hippocampus: physiology / Mice / Neurogenesis:
genetics / Pyramidal Cells: cytology / Pyramidal Cells:
metabolism / DNA methylation (Other) / Dnmt3a (Other) /
adult neurogenesis (Other) / hippocampus (Other) / neuron
maturation (Other)},
cin = {AG Kempermann / AG Toda / Schultze - PRECISE / $R\&D$
PRECISE},
ddc = {570},
cid = {I:(DE-2719)1710001 / I:(DE-2719)1710014 /
I:(DE-2719)1013031 / I:(DE-2719)5000031},
pnm = {352 - Disease Mechanisms (POF4-352) / 354 - Disease
Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34337766},
pmc = {pmc:PMC8441477},
doi = {10.15252/embj.2020107100},
url = {https://pub.dzne.de/record/162864},
}