ArticleThe Journal of biological chemistry2013
Specificity protein 1 (Sp1)-dependent activation of the synapsin I gene (SYN1) is modulated by RE1-silencing transcription factor (REST) and 5'-cytosine-phosphoguanine (CpG) methylation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 61 citations in OpenAlex.
- Resistance of E2F4DN to p38Scientific reports · 2026Article
- Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling.Cell reports · 2026Article
- Integrative bulk and single-cell transcriptomic profiling identifies core gene networks and potential therapeutic targets in glioma.BMC cancer · 2025Article
- Article
- Stroke Causes DNA Methylation atJournal of the American Heart Association · 2024Article
- Overexpression of REST Represses the Epithelial-Mesenchymal Transition Process and Decreases the Aggressiveness of Prostate Cancer Cells.International journal of molecular sciences · 2024Article
- REST-dependent glioma progression occurs independently of the repression of the long non-coding RNA HAR1A.PloS one · 2024Article
- Uncovering the role of FOXA2 in the Development of Human Serotonin Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The alpha-synuclein oligomers activate nuclear factor of activated T-cell (NFAT) modulating synaptic homeostasis and apoptosis.Molecular medicine (Cambridge, Mass.) · 2023Article
- Genome-wide Association Studies of REST Gene Associated Neurological Diseases/traits with Related Single Nucleotide Polymorphisms.Current neurovascular research · 2023Article
- Role of primary aging hallmarks in Alzheimer´s disease.Theranostics · 2023Review
- CRISPR single base editing, neuronal disease modelling and functional genomics for genetic variant analysis: pipeline validation using Kleefstra syndrome EHMT1 haploinsufficiency.Stem cell research & therapy · 2022Article
- REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion.eLife · 2021Article
- Neuroinflammation induces synaptic scaling through IL-1β-mediated activation of the transcriptional repressor REST/NRSF.Cell death & disease · 2021Article
- Article
- DNA Methylation Inhibits the Expression of CFSH in Mud Crab.Frontiers in endocrinology · 2020Article
- Sp1 in Astrocyte Is Important for Neurite Outgrowth and Synaptogenesis.Molecular neurobiology · 2020Article
- Diet-induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity.Food science & nutrition · 2019Review
- Mild Inactivation of RE-1 Silencing Transcription Factor (REST) Reduces Susceptibility to Kainic Acid-Induced Seizures.Frontiers in cellular neuroscience · 2019Article
- In Vitro Neuroprotection of Rat Hippocampal Neurons by Manninotriose and Astragaloside IV Against Corticosterone-Induced Toxicity.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The development and function of the nervous system are directly dependent on a well defined pattern of gene expression. Indeed, perturbation of transcriptional activity or epigenetic modifications of chromatin can dramatically influence neuronal phenotypes. The phosphoprotein synapsin I (Syn I) plays a crucial role during axonogenesis and synaptogenesis as well as in synaptic transmission and plasticity of mature neurons. Abnormalities in SYN1 gene expression have been linked to important neuropsychiatric disorders, such as epilepsy and autism. SYN1 gene transcription is suppressed in non-neural tissues by the RE1-silencing transcription factor (REST); however, the molecular mechanisms that allow the constitutive expression of this genetic region in neurons have not been clarified yet. Herein we demonstrate that a conserved region of human and mouse SYN1 promoters contains cis-sites for the transcriptional activator Sp1 in close proximity to REST binding motifs. Through a series of functional assays, we demonstrate a physical interaction of Sp1 on the SYN1 promoter and show that REST directly inhibits Sp1-mediated transcription, resulting in SYN1 down-regulation. Upon differentiation of neuroblastoma Neuro2a cells, we observe a decrease in endogenous REST and a higher stability of Sp1 on target GC boxes, resulting in an increase of SYN1 transcription. Moreover, methylation of Sp1 cis-sites in the SYN1 promoter region could provide an additional level of transcriptional regulation. Our results introduce Sp1 as a fundamental activator of basal SYN1 gene expression, whose activity is modulated by the neural master regulator REST and CpG methylation.
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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.