title: Chromatin remodeling inactivates activity genes and regulates neural coding.
abstract: Activity-dependent transcription influences neuronal connectivity, but the roles and mechanisms of inactivation of activity-dependent genes have remained poorly understood. Genome-wide analyses in the mouse cerebellum revealed that the nucleosome remodeling and deacetylase (NuRD) complex deposits the histone variant H2A.z at promoters of activity-dependent genes, thereby triggering their inactivation. Purification of translating messenger RNAs from synchronously developing granule neurons (Sync-TRAP) showed that conditional knockout of the core NuRD subunit Chd4 impairs inactivation of activity-dependent genes when neurons undergo dendrite pruning. Chd4 knockout or expression of NuRD-regulated activity genes impairs dendrite pruning. Imaging of behaving mice revealed hyperresponsivity of granule neurons to sensorimotor stimuli upon Chd4 knockout. Our findings define an epigenetic mechanism that inactivates activity-dependent transcription and regulates dendrite patterning and sensorimotor encoding in the brain.
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.|MD-PhD Program, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hill
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Hemberg
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Naveen C
authors.initials: NC
authors.lastname: Reddy
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ha Y
authors.initials: HY
authors.lastname: Cho
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Arden N
authors.initials: AN
authors.lastname: Guthrie
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Oldenborg
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Heiney
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ohmae
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Javier F
authors.initials: JF
authors.lastname: Medina
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Holy
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Azad
authors.initials: A
authors.lastname: Bonni
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology*; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D009707:Nucleosomes; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; C509277:Mi-2beta protein, mouse; D004265:DNA Helicases