RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling

Patricia M. Garay; Alex Chen; Takao Tsukahara; Jean Carlos Rodríguez Díaz; Rafi Kohen; J. Christian Althaus; Margarete A. Wallner; Roman J. Giger; Kevin S. Jones; Michael A. Sutton; Shigeki Iwase

Cell Reports (Aug 2020)

RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling

Patricia M. Garay,
Alex Chen,
Takao Tsukahara,
Jean Carlos Rodríguez Díaz,
Rafi Kohen,
J. Christian Althaus,
Margarete A. Wallner,
Roman J. Giger,
Kevin S. Jones,
Michael A. Sutton,
Shigeki Iwase

Affiliations

Patricia M. Garay: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Alex Chen: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Takao Tsukahara: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Jean Carlos Rodríguez Díaz: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Rafi Kohen: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA
J. Christian Althaus: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA
Margarete A. Wallner: College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, MI 48109, USA
Roman J. Giger: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA; Cellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, 48109, USA; Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
Kevin S. Jones: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
Michael A. Sutton: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author
Shigeki Iwase: Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author

Journal volume & issue: Vol. 32, no. 6
p. 108002

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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