[HTML][HTML] REST, a master transcriptional regulator in neurodegenerative disease
JY Hwang, RS Zukin - Current opinion in neurobiology, 2018 - Elsevier
JY Hwang, RS Zukin
Current opinion in neurobiology, 2018•ElsevierHighlights•Identified as a master regulator of neuronal genes in embryogenesis, REST is a
common theme in neurodegeneration.•Whereas bioinformatics predicts∼ 2000 REST
targets, a small subset are transcriptionally responsive.•The gene silencing transcription
factor REST not only silences, but also activates gene transcription.•Whereas REST
orchestrates fine-tuning of plasticity genes during development, it represses stress genes in
aging neurons.•Whereas REST promotes death of insulted adult neurons, it protects aged …
common theme in neurodegeneration.•Whereas bioinformatics predicts∼ 2000 REST
targets, a small subset are transcriptionally responsive.•The gene silencing transcription
factor REST not only silences, but also activates gene transcription.•Whereas REST
orchestrates fine-tuning of plasticity genes during development, it represses stress genes in
aging neurons.•Whereas REST promotes death of insulted adult neurons, it protects aged …
Highlights
- Identified as a master regulator of neuronal genes in embryogenesis, REST is a common theme in neurodegeneration.
- Whereas bioinformatics predicts∼ 2000 REST targets, a small subset are transcriptionally responsive.
- The gene silencing transcription factor REST not only silences, but also activates gene transcription.
- Whereas REST orchestrates fine-tuning of plasticity genes during development, it represses stress genes in aging neurons.
- Whereas REST promotes death of insulted adult neurons, it protects aged neurons.
The restrictive element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor (NRSF) is a transcriptional repressor which acts via epigenetic remodeling to silence target genes. Emerging evidence indicates that REST is a master transcriptional regulator of neuron-specific genes not only in neurogenesis and neuronal differentiation, but also in differentiated neurons during the critical period in postnatal brain development, where it plays a role in fine-tuning of genes involved in synaptic plasticity, and in normal aging, where it promotes neuroprotection by repressing genes involved in oxidative stress and β-amyloid toxicity. This review focuses on recent findings that dysregulation of REST and REST-dependent epigenetic remodeling provide a central mechanism critical to the progressive neurodegeneration associated with neurologic disorders and diseases including global ischemia, stroke, epilepsy, Alzheimer's and Huntington's disease.
Elsevier