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. |