Title |
Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor
|
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, December 2015
|
DOI | 10.1073/pnas.1507355112 |
Pubmed ID | |
Authors |
Francesco Paonessa, Stefania Criscuolo, Silvio Sacchetti, Davide Amoroso, Helena Scarongella, Federico Pecoraro Bisogni, Emanuele Carminati, Giacomo Pruzzo, Luca Maragliano, Fabrizia Cesca, Fabio Benfenati |
Abstract |
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 (RE1)-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 light-oxygen-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(+)-channel 1.2 and brain-derived neurotrophic factor transcription and boosted Na(+) 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. |
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Country | Count | As % |
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France | 1 | 14% |
Japan | 1 | 14% |
Unknown | 5 | 71% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 57% |
Science communicators (journalists, bloggers, editors) | 2 | 29% |
Practitioners (doctors, other healthcare professionals) | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | <1% |
Germany | 1 | <1% |
Austria | 1 | <1% |
Unknown | 112 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 27 | 23% |
Researcher | 21 | 18% |
Student > Master | 12 | 10% |
Student > Bachelor | 11 | 10% |
Student > Doctoral Student | 8 | 7% |
Other | 17 | 15% |
Unknown | 19 | 17% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 26 | 23% |
Biochemistry, Genetics and Molecular Biology | 25 | 22% |
Neuroscience | 20 | 17% |
Medicine and Dentistry | 4 | 3% |
Materials Science | 3 | 3% |
Other | 14 | 12% |
Unknown | 23 | 20% |