ArticleProceedings of the National Academy of Sciences of the United States of America2016
Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Phosphorylation by CaMKIV regulates the transcriptional repressor activity and half-life of REST/NRSF.Science advances · 2026Article
- Induced Neural Progenitor Specification from Human Pluripotent Stem Cells by a Refined Synthetic Notch Platform.ACS synthetic biology · 2025Article
- Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT.Nature chemical biology · 2025Article
- In vivo optogenetic manipulations of endogenous proteins reveal spatiotemporal roles of microtubule and kinesin in dendrite patterning.Science advances · 2024Article
- FAK-LINC01089 negative regulatory loop controls chemoresistance and progression of small cell lung cancer.Oncogene · 2024Article
- REST Is Not Resting: REST/NRSF in Health and Disease.Biomolecules · 2023Review
- Towards translational optogenetics.Nature biomedical engineering · 2023Review
- Electron microscopy reveals toroidal shape of master neuronal cell differentiator REST - RE1-silencing transcription factor.Computational and structural biotechnology journal · 2023Article
- Optogenetic Application to Investigating Cell Behavior and Neurological Disease.Frontiers in cellular neuroscience · 2022Review
- REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion.eLife · 2021Article
- A guide to the optogenetic regulation of endogenous molecules.Nature methods · 2021Review
- New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Single-component near-infrared optogenetic systems for gene transcription regulation.Nature communications · 2021Article
- Article
- A light way for nuclear cell biologists.Journal of biochemistry · 2021Review
- Engineering an Allosteric Control of Protein Function.The journal of physical chemistry. B · 2021Review
- Photoreaction Mechanisms of Flavoprotein Photoreceptors and Their Applications.Advances in experimental medicine and biology · 2021Review
- Article
- LINC01198 facilitates gliomagenesis through activating PI3K/AKT pathway.RNA biology · 2020Article
- ANeural plasticity · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.