| Literature DB >> 27418512 |
Yue Yang1, Tomoko Yamada1, Kelly K Hill1,2, Martin Hemberg3, Naveen C Reddy1, Ha Y Cho1, Arden N Guthrie1, Anna Oldenborg1, Shane A Heiney4, Shogo Ohmae4, Javier F Medina4, Timothy E Holy1, Azad Bonni1.
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.Entities:
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Year: 2016 PMID： 27418512 PMCID： PMC4993111 DOI： 10.1126/science.aad4225
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728