Chromatin remodeling inactivates activity genes and regulates neural coding

Yue Yang; Tomoko Yamada; Kelly K 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

doi:10.1126/science.aad4225

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Chromatin remodeling inactivates activity genes and regulates neural coding

Journal article

Open access

Peer reviewed

Chromatin remodeling inactivates activity genes and regulates neural coding

Yue Yang, Tomoko Yamada, Kelly K Hill, Martin Hemberg, Naveen C Reddy, Ha Y Cho, Arden N Guthrie, Anna Oldenborg, Shane A Heiney, Shogo Ohmae, …

Science (American Association for the Advancement of Science), Vol.353(6296), pp.300-305

07/15/2016

DOI: 10.1126/science.aad4225

PMCID: PMC4993111

PMID: 27418512

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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 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.

Animals

Cerebellum - physiology

Chromatin Assembly and Disassembly

Dendrites - physiology

DNA Helicases - metabolism

Gene Knockout Techniques

Gene Silencing

Genome-Wide Association Study

Histones - metabolism

Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism

Mice

Mice, Knockout

Neurons - physiology

Nucleosomes - metabolism

Promoter Regions, Genetic

Transcription, Genetic

Details

Title: Subtitle: Chromatin remodeling inactivates activity genes and regulates neural coding
Creators: Yue Yang - Washington University in St. Louis
Tomoko Yamada - Washington University in St. Louis
Kelly K Hill - Washington University in St. Louis
Martin Hemberg - Wellcome Sanger Institute
Naveen C Reddy - Washington University in St. Louis
Ha Y Cho - Washington University in St. Louis
Arden N Guthrie - Washington University in St. Louis
Anna Oldenborg - Washington University in St. Louis
Shane A Heiney - Baylor College of Medicine
Shogo Ohmae - Baylor College of Medicine
Javier F Medina - Baylor College of Medicine
Timothy E Holy - Washington University in St. Louis
Azad Bonni - Washington University in St. Louis
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.353(6296), pp.300-305
DOI: 10.1126/science.aad4225
PMID: 27418512
PMCID: PMC4993111
NLM abbreviation: Science
ISSN: 0036-8075
eISSN: 1095-9203
Grant note: UL1TR000448 / NCATS NIH HHS R01 NS068409 / NINDS NIH HHS MH093727 / NIMH NIH HHS T32 GM07200 / NIGMS NIH HHS P30 CA091842 / NCI NIH HHS P30 CA91842 / NCI NIH HHS T32 GM007200 / NIGMS NIH HHS UL1 TR000448 / NCATS NIH HHS NS041021 / NINDS NIH HHS R01 NS041021 / NINDS NIH HHS
Language: English
Date published: 07/15/2016
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984622752302771

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