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Chromatin remodeling inactivates activity genes and regulates neural coding

2016; American Association for the Advancement of Science; Volume: 353; Issue: 6296 Linguagem: Inglês

10.1126/science.aad4225

1095-9203

Yue Yang, Tomoko Yamada, Kelly Hill, Martin Hemberg, Naveen C. Reddy, Ha Y. Cho, Arden N. Guthrie, Anna Oldenborg, Shane A. Heiney, Shogo Ohmae, Javier F. Medina, Timothy E. Holy, Azad Bonni,

RNA Research and Splicing

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.