Chromatin remodeling inactivates activity genes and regulates neural coding.
Chromatin remodeling inactivates activity genes and regulates neural coding.
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染色质重塑使活性基因失活并调节神经编码。
DOI：
10.1126/science.aad4225
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发表时间：
2016-07-15
期刊：
影响因子：
--
通讯作者：
Bonni A
中科院分区：
文献类型：
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作者：
Yang Y;Yamada T;Hill KK;Hemberg M;Reddy NC;Cho HY;Guthrie AN;Oldenborg A;Heiney SA;Ohmae S;Medina JF;Holy TE;Bonni A
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 mRNAs 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.
