The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes

The mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenu...

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Main Authors:	Shawn McClelland, Gary P Brennan, Celine Dubé, Seeta Rajpara, Shruti Iyer, Cristina Richichi, Christophe Bernard, Tallie Z Baram
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2014-08-01
Series:	eLife
Subjects:	neuron-restrictive silencing factor epilepsy gene set enrichment analysi
Online Access:	https://elifesciences.org/articles/01267

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spelling	doaj-1988140a94ad4323a2aba1f399965d382021-05-04T23:24:40ZengeLife Sciences Publications LtdeLife2050-084X2014-08-01310.7554/eLife.01267The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genesShawn McClelland0Gary P Brennan1Celine Dubé2Seeta Rajpara3Shruti Iyer4Cristina Richichi5Christophe Bernard6Tallie Z Baram7Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States; Department of Pediatrics, University of California, Irvine, Irvine, United States; Department of Neurology, University of California, Irvine, Irvine, United StatesDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States; Department of Pediatrics, University of California, Irvine, Irvine, United States; Department of Neurology, University of California, Irvine, Irvine, United StatesDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States; Department of Pediatrics, University of California, Irvine, Irvine, United States; Department of Neurology, University of California, Irvine, Irvine, United StatesDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States; Department of Pediatrics, University of California, Irvine, Irvine, United States; Department of Neurology, University of California, Irvine, Irvine, United StatesDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States; Department of Pediatrics, University of California, Irvine, Irvine, United States; Department of Neurology, University of California, Irvine, Irvine, United StatesDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States; Department of Pediatrics, University of California, Irvine, Irvine, United States; Department of Neurology, University of California, Irvine, Irvine, United StatesLaboratoire Epilepsie et Cognition, Institut National de la Santé et de la Recherche Médicale, Marseille, FranceDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States; Department of Pediatrics, University of California, Irvine, Irvine, United States; Department of Neurology, University of California, Irvine, Irvine, United StatesThe mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenuated development of this disorder. In this study, we found that epilepsy-provoking seizures increased the low NRSF levels in mature hippocampus several fold yet surprisingly, provoked repression of only a subset (∼10%) of potential NRSF target genes. Accordingly, the repressed gene-set was rescued when NRSF binding to chromatin was blocked. Unexpectedly, genes selectively repressed by NRSF had mid-range binding frequencies to the repressor, a property that rendered them sensitive to moderate fluctuations of NRSF levels. Genes selectively regulated by NRSF during epileptogenesis coded for ion channels, receptors, and other crucial contributors to neuronal function. Thus, dynamic, selective regulation of NRSF target genes may play a role in influencing neuronal properties in pathological and physiological contexts.https://elifesciences.org/articles/01267neuron-restrictive silencing factorepilepsygene set enrichment analysi
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Shawn McClelland Gary P Brennan Celine Dubé Seeta Rajpara Shruti Iyer Cristina Richichi Christophe Bernard Tallie Z Baram
spellingShingle	Shawn McClelland Gary P Brennan Celine Dubé Seeta Rajpara Shruti Iyer Cristina Richichi Christophe Bernard Tallie Z Baram The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes eLife neuron-restrictive silencing factor epilepsy gene set enrichment analysi
author_facet	Shawn McClelland Gary P Brennan Celine Dubé Seeta Rajpara Shruti Iyer Cristina Richichi Christophe Bernard Tallie Z Baram
author_sort	Shawn McClelland
title	The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes
title_short	The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes
title_full	The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes
title_fullStr	The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes
title_full_unstemmed	The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes
title_sort	transcription factor nrsf contributes to epileptogenesis by selective repression of a subset of target genes
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2014-08-01
description	The mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenuated development of this disorder. In this study, we found that epilepsy-provoking seizures increased the low NRSF levels in mature hippocampus several fold yet surprisingly, provoked repression of only a subset (∼10%) of potential NRSF target genes. Accordingly, the repressed gene-set was rescued when NRSF binding to chromatin was blocked. Unexpectedly, genes selectively repressed by NRSF had mid-range binding frequencies to the repressor, a property that rendered them sensitive to moderate fluctuations of NRSF levels. Genes selectively regulated by NRSF during epileptogenesis coded for ion channels, receptors, and other crucial contributors to neuronal function. Thus, dynamic, selective regulation of NRSF target genes may play a role in influencing neuronal properties in pathological and physiological contexts.
topic	neuron-restrictive silencing factor epilepsy gene set enrichment analysi
url	https://elifesciences.org/articles/01267
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The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes

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