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

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

Research output: Contribution to journal › Article › peer-review

87 Scopus citations

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.

Original language	English
Pages (from-to)	300-306
Number of pages	7
Journal	Science
Volume	353
Issue number	6296
DOIs	https://doi.org/10.1126/science.aad4225
State	Published - Jul 15 2016

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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",

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T1 - Chromatin remodeling inactivates Activity genes and regulates neural coding

AU - Yang, Yue

AU - Yamada, Tomoko

AU - Hill, Kelly K.

AU - Hemberg, Martin

AU - Reddy, Naveen C.

AU - Cho, Ha Y.

AU - Guthrie, Arden N.

AU - Oldenborg, Anna

AU - Heiney, Shane A.

AU - Ohmae, Shogo

AU - Medina, Javier F.

AU - Holy, Timothy E.

AU - Bonni, Azad

PY - 2016/7/15

Y1 - 2016/7/15

N2 - 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.

AB - 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.

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SN - 0036-8075

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EP - 306

JO - Science

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IS - 6296

ER -

Chromatin remodeling inactivates Activity genes and regulates neural coding

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