TY  - JOUR
AU  - Zocher, Sara
AU  - Overall, Rupert
AU  - Berdugo-Vega, Gabriel
AU  - Rund, Nicole
AU  - Karasinsky, Anne
AU  - Adusumilli, Vijay S
AU  - Steinhauer, Christina
AU  - Scheibenstock, Sina
AU  - Händler, Kristian
AU  - Schultze, Joachim L
AU  - Calegari, Federico
AU  - Kempermann, Gerd
TI  - De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.
JO  - The EMBO journal
VL  - 40
IS  - 18
SN  - 1460-2075
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2021-01519
SP  - e107100
PY  - 2021
AB  - 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.
KW  - Animals
KW  - Cell Differentiation: genetics
KW  - Cells, Cultured
KW  - DNA Methylation
KW  - Epigenesis, Genetic
KW  - Gene Expression Regulation
KW  - Hippocampus: physiology
KW  - Mice
KW  - Neurogenesis: genetics
KW  - Pyramidal Cells: cytology
KW  - Pyramidal Cells: metabolism
KW  - DNA methylation (Other)
KW  - Dnmt3a (Other)
KW  - adult neurogenesis (Other)
KW  - hippocampus (Other)
KW  - neuron maturation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34337766
C2  - pmc:PMC8441477
DO  - DOI:10.15252/embj.2020107100
UR  - https://pub.dzne.de/record/162864
ER  -