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RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling

Long-lasting forms of synaptic plasticity such as synaptic scaling are critically dependent on transcription. Activity-dependent transcriptional dynamics in neurons, however, remain incompletely characterized because most previous efforts relied on measurement of steady-state mRNAs. Here, we use nas...

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Autores principales: Garay, Patricia M., Chen, Alex, Tsukahara, Takao, Rodríguez Díaz, Jean Carlos, Kohen, Rafi, Althaus, J. Christian, Wallner, Margarete A., Giger, Roman J., Jones, Kevin S., Sutton, Michael A., Iwase, Shigeki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418709/
https://www.ncbi.nlm.nih.gov/pubmed/32783930
http://dx.doi.org/10.1016/j.celrep.2020.108002
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author Garay, Patricia M.
Chen, Alex
Tsukahara, Takao
Rodríguez Díaz, Jean Carlos
Kohen, Rafi
Althaus, J. Christian
Wallner, Margarete A.
Giger, Roman J.
Jones, Kevin S.
Sutton, Michael A.
Iwase, Shigeki
author_facet Garay, Patricia M.
Chen, Alex
Tsukahara, Takao
Rodríguez Díaz, Jean Carlos
Kohen, Rafi
Althaus, J. Christian
Wallner, Margarete A.
Giger, Roman J.
Jones, Kevin S.
Sutton, Michael A.
Iwase, Shigeki
author_sort Garay, Patricia M.
collection PubMed
description Long-lasting forms of synaptic plasticity such as synaptic scaling are critically dependent on transcription. Activity-dependent transcriptional dynamics in neurons, however, remain incompletely characterized because most previous efforts relied on measurement of steady-state mRNAs. Here, we use nascent RNA sequencing to profile transcriptional dynamics of primary neuron cultures undergoing network activity shifts. We find pervasive transcriptional changes, in which ∼45% of expressed genes respond to network activity shifts. We further link retinoic acid-induced 1 (RAI1), the Smith-Magenis syndrome gene, to the transcriptional program driven by reduced network activity. Remarkable agreement among nascent transcriptomes, dynamic chromatin occupancy of RAI1, and electrophysiological properties of Rai1-deficient neurons demonstrates the essential roles of RAI1 in suppressing synaptic upscaling in the naive network, while promoting upscaling triggered by activity silencing. These results highlight the utility of bona fide transcription profiling to discover mechanisms of activity-dependent chromatin remodeling that underlie normal and pathological synaptic plasticity.
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spelling pubmed-74187092020-08-12 RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling Garay, Patricia M. Chen, Alex Tsukahara, Takao Rodríguez Díaz, Jean Carlos Kohen, Rafi Althaus, J. Christian Wallner, Margarete A. Giger, Roman J. Jones, Kevin S. Sutton, Michael A. Iwase, Shigeki Cell Rep Article Long-lasting forms of synaptic plasticity such as synaptic scaling are critically dependent on transcription. Activity-dependent transcriptional dynamics in neurons, however, remain incompletely characterized because most previous efforts relied on measurement of steady-state mRNAs. Here, we use nascent RNA sequencing to profile transcriptional dynamics of primary neuron cultures undergoing network activity shifts. We find pervasive transcriptional changes, in which ∼45% of expressed genes respond to network activity shifts. We further link retinoic acid-induced 1 (RAI1), the Smith-Magenis syndrome gene, to the transcriptional program driven by reduced network activity. Remarkable agreement among nascent transcriptomes, dynamic chromatin occupancy of RAI1, and electrophysiological properties of Rai1-deficient neurons demonstrates the essential roles of RAI1 in suppressing synaptic upscaling in the naive network, while promoting upscaling triggered by activity silencing. These results highlight the utility of bona fide transcription profiling to discover mechanisms of activity-dependent chromatin remodeling that underlie normal and pathological synaptic plasticity. The Authors. 2020-08-11 2020-08-11 /pmc/articles/PMC7418709/ /pubmed/32783930 http://dx.doi.org/10.1016/j.celrep.2020.108002 Text en © 2020 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Garay, Patricia M.
Chen, Alex
Tsukahara, Takao
Rodríguez Díaz, Jean Carlos
Kohen, Rafi
Althaus, J. Christian
Wallner, Margarete A.
Giger, Roman J.
Jones, Kevin S.
Sutton, Michael A.
Iwase, Shigeki
RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling
title RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling
title_full RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling
title_fullStr RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling
title_full_unstemmed RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling
title_short RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling
title_sort rai1 regulates activity-dependent nascent transcription and synaptic scaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418709/
https://www.ncbi.nlm.nih.gov/pubmed/32783930
http://dx.doi.org/10.1016/j.celrep.2020.108002
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