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000162864 041__ $$aEnglish
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000162864 1001_ $$0P:(DE-2719)2810548$$aZocher, Sara$$b0$$eFirst author
000162864 245__ $$aDe novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.
000162864 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2021
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000162864 520__ $$aAdult 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.
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000162864 650_7 $$2Other$$aDNA methylation
000162864 650_7 $$2Other$$aDnmt3a
000162864 650_7 $$2Other$$aadult neurogenesis
000162864 650_7 $$2Other$$ahippocampus
000162864 650_7 $$2Other$$aneuron maturation
000162864 650_2 $$2MeSH$$aAnimals
000162864 650_2 $$2MeSH$$aCell Differentiation: genetics
000162864 650_2 $$2MeSH$$aCells, Cultured
000162864 650_2 $$2MeSH$$aDNA Methylation
000162864 650_2 $$2MeSH$$aEpigenesis, Genetic
000162864 650_2 $$2MeSH$$aGene Expression Regulation
000162864 650_2 $$2MeSH$$aHippocampus: physiology
000162864 650_2 $$2MeSH$$aMice
000162864 650_2 $$2MeSH$$aNeurogenesis: genetics
000162864 650_2 $$2MeSH$$aPyramidal Cells: cytology
000162864 650_2 $$2MeSH$$aPyramidal Cells: metabolism
000162864 7001_ $$0P:(DE-2719)2812530$$aOverall, Rupert$$b1
000162864 7001_ $$aBerdugo-Vega, Gabriel$$b2
000162864 7001_ $$0P:(DE-2719)2811674$$aRund, Nicole$$b3
000162864 7001_ $$0P:(DE-2719)9001964$$aKarasinsky, Anne$$b4$$udzne
000162864 7001_ $$0P:(DE-2719)2810887$$aAdusumilli, Vijay S$$b5
000162864 7001_ $$0P:(DE-2719)2812839$$aSteinhauer, Christina$$b6
000162864 7001_ $$0P:(DE-2719)9001974$$aScheibenstock, Sina$$b7$$udzne
000162864 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b8
000162864 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b9
000162864 7001_ $$00000-0002-3703-2802$$aCalegari, Federico$$b10
000162864 7001_ $$0P:(DE-2719)2000011$$aKempermann, Gerd$$b11$$eLast author
000162864 773__ $$0PERI:(DE-600)1467419-1$$a10.15252/embj.2020107100$$gVol. 40, no. 18$$n18$$pe107100$$tThe EMBO journal$$v40$$x1460-2075$$y2021
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