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Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.

Optogenetics provides new ways to activate gene transcription; however, no attempts have been made as yet to modulate mammalian transcription factors. We report the light-mediated regulation of the repressor element 1 (REI)-silencing transcription factor (REST), a master regulator of neural genes. T... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America January 5, 2016, Vol.113(1), pp.E91-100
Main Author: Paonessa, Francesco
Other Authors: Criscuolo, Stefania , Sacchetti, Silvio , Amoroso, Davide , Scarongella, Helena , Pecoraro Bisogni, Federico , Carminati, Emanuele , Pruzzo, Giacomo , Maragliano, Luca , Cesca, Fabrizia , Benfenati, Fabio
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1507355112
Link: http://search.proquest.com/docview/1754525950/?pq-origsite=primo
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title: Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.
format: Article
creator:
  • Paonessa, Francesco
  • Criscuolo, Stefania
  • Sacchetti, Silvio
  • Amoroso, Davide
  • Scarongella, Helena
  • Pecoraro Bisogni, Federico
  • Carminati, Emanuele
  • Pruzzo, Giacomo
  • Maragliano, Luca
  • Cesca, Fabrizia
  • Benfenati, Fabio
subjects:
  • Animals–Genetics
  • Avena–Metabolism
  • Cell Line, Tumor–Chemistry
  • Chromatin–Metabolism
  • DNA–Methods
  • Electrophoretic Mobility Shift Assay–Genetics
  • Gene Expression Regulation–Genetics
  • Mice–Metabolism
  • Neurons–Antagonists & Inhibitors
  • Optogenetics–Chemistry
  • Plant Proteins–Genetics
  • Protein Binding–Genetics
  • Protein Structure, Tertiary–Genetics
  • Recombinant Fusion Proteins–Genetics
  • Repressor Proteins–Genetics
  • Transcription, Genetic–Genetics
  • Transduction, Genetic–Genetics
  • Chromatin
  • Plant Proteins
  • Re1-Silencing Transcription Factor
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • DNA
  • Aslov2
  • Rest/Nrsf
  • Gene Transcription
  • Molecular Dynamics
  • Optogenetics
ispartof: Proceedings of the National Academy of Sciences of the United States of America, January 5, 2016, Vol.113(1), pp.E91-100
description: Optogenetics provides new ways to activate gene transcription; however, no attempts have been made as yet to modulate mammalian transcription factors. We report the light-mediated regulation of the repressor element 1 (REI)-silencing transcription factor (REST), a master regulator of neural genes. To tune REST activity, we selected two protein domains that impair REST-DNA binding or recruitment of the cofactor mSin3a. Computational modeling guided the fusion of the inhibitory domains to the light-sensitive Avena sativa lightoxygen-voltage-sensing (LOV) 2-phototrophin 1 (AsLOV2). By expressing AsLOV2 chimeras in Neuro2a cells, we achieved light-dependent modulation of REST target genes that was associated with an improved neural differentiation. In primary neurons, light-mediated REST inhibition increased [Na.sup.+]-channel 1.2 and brain-derived neurotrophic factor transcription and boosted [Na.sup.+] currents and neuronal firing. This optogenetic approach allows the coordinated expression of a cluster of genes impinging on neuronal activity, providing a tool for studying neuronal physiology and correcting gene expression changes taking place in brain diseases. optogenetics | AsLOV2 | REST/NRSF | gene transcription | molecular dynamics
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1507355112
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleRegulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.
creatorPaonessa, Francesco ; Criscuolo, Stefania ; Sacchetti, Silvio ; Amoroso, Davide ; Scarongella, Helena ; Pecoraro Bisogni, Federico ; Carminati, Emanuele ; Pruzzo, Giacomo ; Maragliano, Luca ; Cesca, Fabrizia ; Benfenati, Fabio
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ispartofProceedings of the National Academy of Sciences of the United States of America, January 5, 2016, Vol.113(1), pp.E91-100
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1507355112
subjectAnimals–Genetics ; Avena–Metabolism ; Cell Line, Tumor–Chemistry ; Chromatin–Metabolism ; DNA–Methods ; Electrophoretic Mobility Shift Assay–Genetics ; Gene Expression Regulation–Genetics ; Mice–Metabolism ; Neurons–Antagonists & Inhibitors ; Optogenetics–Chemistry ; Plant Proteins–Genetics ; Protein Binding–Genetics ; Protein Structure, Tertiary–Genetics ; Recombinant Fusion Proteins–Genetics ; Repressor Proteins–Genetics ; Transcription, Genetic–Genetics ; Transduction, Genetic–Genetics ; Chromatin ; Plant Proteins ; Re1-Silencing Transcription Factor ; Recombinant Fusion Proteins ; Repressor Proteins ; DNA ; Aslov2 ; Rest/Nrsf ; Gene Transcription ; Molecular Dynamics ; Optogenetics
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descriptionOptogenetics provides new ways to activate gene transcription; however, no attempts have been made as yet to modulate mammalian transcription factors. We report the light-mediated regulation of the repressor element 1 (REI)-silencing transcription factor (REST), a master regulator of neural genes. To tune REST activity, we selected two protein domains that impair REST-DNA binding or recruitment of the cofactor mSin3a. Computational modeling guided the fusion of the inhibitory domains to the light-sensitive Avena sativa lightoxygen-voltage-sensing (LOV) 2-phototrophin 1 (AsLOV2). By expressing AsLOV2 chimeras in Neuro2a cells, we achieved light-dependent modulation of REST target genes that was associated with an improved neural differentiation. In primary neurons, light-mediated REST inhibition increased [Na.sup.+]-channel 1.2 and brain-derived neurotrophic factor transcription and boosted [Na.sup.+] currents and neuronal firing. This optogenetic approach allows the coordinated expression of a cluster of genes impinging on neuronal activity, providing a tool for studying neuronal physiology and correcting gene expression changes taking place in brain diseases. optogenetics | AsLOV2 | REST/NRSF | gene transcription | molecular dynamics
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titleRegulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.
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titleRegulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.
authorPaonessa, Francesco ; Criscuolo, Stefania ; Sacchetti, Silvio ; Amoroso, Davide ; Scarongella, Helena ; Pecoraro Bisogni, Federico ; Carminati, Emanuele ; Pruzzo, Giacomo ; Maragliano, Luca ; Cesca, Fabrizia ; Benfenati, Fabio
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6Gene Expression Regulation–Genetics
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16Transduction, Genetic–Genetics
17Chromatin
18Plant Proteins
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21Repressor Proteins
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