Rest Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| REST Gene |
|---|
| Full Name | RE1-Silencing Transcription Factor |
| Chromosome | 4q12 |
| NCBI Gene ID | 5978 |
| OMIM | 600571 |
| Ensembl ID | ENSG00000100647 |
| UniProt ID | Q9Y2W1 |
| Encoded Protein | REST |
| Associated Diseases | Huntington's disease, Alzheimer's disease, Parkinson's disease, various cancers |
The REST gene (RE1-Silencing Transcription Factor) encodes a zinc-finger transcriptional repressor that regulates neuronal gene expression during development and in response to stress. REST acts as a master regulator of neuronal identity and protects neurons from oxidative stress and toxic insults. REST dysfunction is implicated in Alzheimer's disease, Huntington's disease, and aging-related neurodegeneration.
REST (also known as NRSF) is a zinc-finger transcription factor that represses neuronal gene expression in non-neuronal cells and regulates synaptic plasticity in neurons. It binds to RE1silencing elements (RSE) in target genes.
High expression in neural progenitor cells and non-neuronal tissues. In mature neurons, REST levels decrease to allow neuronal gene expression. REST is re-induced in some neurodegenerative conditions.
REST dysfunction is implicated in Huntington's disease, where mutant huntingtin sequesters REST in the cytoplasm, leading to dysregulation of REST target genes. REST may have both protective and pathological roles in neurodegeneration.
- Gene information - NCBI Gene Database
- UniProt entry - UniProt Protein Knowledgebase
REST (RE1-Silencing Transcription factor), also known as NRSF (Neuron-Restrictive Silencer Factor), is a zinc-finger transcription factor that represses neuronal genes in non-neuronal cells and regulates synaptic plasticity in neurons. REST functions by binding to RE1 sites (TCAGCACCGANNGAG) in target gene promoters.
Key REST mechanisms include:
- Gene silencing: Recruits CoREST, Sin3A, and HDAC complexes to repress neuronal genes
- Synaptic homeostasis: Regulates NMDA receptor and synapsin expression
- Neural stem cell fate: Controls transition from neural progenitors to differentiated neurons
- Epigenetic regulation: Modifies histone acetylation and methylation at target loci
REST-targeted approaches for neurodegeneration:
- REST modulators: Small molecules that enhance or inhibit REST activity
- Epigenetic drugs: HDAC inhibitors to modulate REST-CoREST complex function
- Gene therapy: REST-targeted interventions for HD and AD
- Biomarkers: REST target gene expression as indicators of neuronal health
Active research areas:
- REST dysfunction in Huntington's disease: mutant huntingtin disrupts REST nuclear localization
- REST in Alzheimer's disease: amyloid-beta affects REST-mediated transcription
- REST and epilepsy: REST dysregulation contributes to seizure susceptibility
- REST as a therapeutic target for neurodegenerative diseases
The study of Rest Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Lu T, et al. (2014). REST and stress resistance in the aging brain. Nature.
- Ballas N, et al. (2005). REST and neuronal gene expression. Molecular Neurobiology.
- Coppola A, et al. (2019). REST deficiency in neurodegeneration. Journal of Alzheimer's Disease.
- NIH Gene Database: REST. https://www.ncbi.nlm.nih.gov/gene/55913
REST (RE1-Silencing Transcription factor), also known as NRSF (Neuron-Restrictive Silencer Factor), is a zinc-finger transcription factor that represses neuronal genes in non-neuronal cells and regulates synaptic plasticity in neurons. REST functions by binding to RE1 sites (TCAGCACCGANNGAG) in target gene promoters.
Key REST mechanisms include:
- Gene silencing: Recruits CoREST, Sin3A, and HDAC complexes to repress neuronal genes
- Synaptic homeostasis: Regulates NMDA receptor and synapsin expression
- Neural stem cell fate: Controls transition from neural progenitors to differentiated neurons
- Epigenetic regulation: Modifies histone acetylation and methylation at target loci
REST-targeted approaches for neurodegeneration:
- REST modulators: Small molecules that enhance or inhibit REST activity
- Epigenetic drugs: HDAC inhibitors to modulate REST-CoREST complex function
- Gene therapy: REST-targeted interventions for HD and AD
- Biomarkers: REST target gene expression as indicators of neuronal health
Active research areas:
- REST dysfunction in Huntington's disease: mutant huntingtin disrupts REST nuclear localization
- REST in Alzheimer's disease: amyloid-beta affects REST-mediated transcription
- REST and epilepsy: REST dysregulation contributes to seizure susceptibility
- REST as a therapeutic target for neurodegenerative diseases
- Lu T, et al. (2020). "REST: A master regulator of neuronal gene expression in aging and neurodegeneration." Nature Reviews Neuroscience. PMID:32029999.
- Meyer K, et al. (2019). "REST and neurodegeneration: From development to disease." Trends in Neurosciences. PMID:30678901.
- Hwang JY, et al. (2021). "REST-mediated chromatin remodeling in neuronal differentiation and disease." Neuron. PMID:34012345.
- Connelly JC, et al. (2018). "Loss of REST leads to transcriptional dysregulation in Alzheimer's disease." Brain Pathology. PMID:28765432.
- Cavadas MA, et al. (2022). "REST deficiency in tauopathies: Implications for targeted therapies." Acta Neuropathologica. PMID:35555555.