@article{2dac46e6c44d4324b13aad04c728a276,
title = "Chromatin remodeling inactivates Activity genes and regulates neural coding",
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 activitydependent genes, thereby triggering their inactivation. Purification of translating messenger RNAs from synchronously developing granule neurons (Sync-TRAP) showed that conditional knockout of the coreNuRD 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 behavingmice 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.",
author = "Yue Yang and Tomoko Yamada and Hill, {Kelly K.} and Martin Hemberg and Reddy, {Naveen C.} and Cho, {Ha Y.} and Guthrie, {Arden N.} and Anna Oldenborg and Heiney, {Shane A.} and Shogo Ohmae and Medina, {Javier F.} and Holy, {Timothy E.} and Azad Bonni",
note = "Funding Information: We thank members of the Bonni laboratory for helpful discussions and critical reading of the manuscript and E. Han for advice in imaging analyses. Supported by NIH grant NS041021 (A.B.), the Mathers Foundation (A.B.), NIH grant MH093727 (J.F.M.), and NIH Medical Scientist Training Program grant T32 GM07200 (K.K.H.). We thank the Genome Technology Access Center at Washington University, which is supported by National Cancer Institute grant P30 CA91842 to the Siteman Cancer Center and by Institute of Clinical and Translational Sciences-Clinical and Translational Science Awards UL1TR000448. The authors declare no conflicts of interest. Raw sequencing data related to this study have been archived in the Gene Expression Omnibus (GEO) database under accession number GSE83253 (available at www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83253). Publisher Copyright: Copyright 2016 by the American Association for the Advancement of Science; all rights reserved.",
year = "2016",
month = jul,
day = "15",
doi = "10.1126/science.aad4225",
language = "English",
volume = "353",
pages = "300--306",
journal = "Science",
issn = "0036-8075",
number = "6296",
}