De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.

Autor: Zocher S; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Overall RW; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Berdugo-Vega G; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Rund N; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Karasinsky A; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Adusumilli VS; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Steinhauer C; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Scheibenstock S; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Händler K; PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany., Schultze JL; PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany., Calegari F; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Kempermann G; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2021 Sep 15; Vol. 40 (18), pp. e107100. Date of Electronic Publication: 2021 Aug 02.
DOI: 10.15252/embj.2020107100
Abstrakt: 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.
(© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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