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Publication : Chromatin remodeling inactivates activity genes and regulates neural coding.

First Author  Yang Y Year  2016
Journal  Science Volume  353
Issue  6296 Pages  300-305
PubMed ID  27418512 Mgi Jnum  J:233819
Mgi Id  MGI:5788187 Doi  10.1126/science.aad4225
Citation  Yang Y, et al. (2016) Chromatin remodeling inactivates activity genes and regulates neural coding. Science 353(6296):300-5
abstractText  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.
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