ArticleTranslational psychiatry2022
NRSF/REST lies at the intersection between epigenetic regulation, miRNA-mediated gene control and neurodevelopmental pathways associated with Intellectual disability (ID) and Schizophrenia.
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Trigger-day hCG effects on DNA methylation and neurodevelopment in ART offspring.Nature communications · 2026Article
- REST deficiency and neurogenic-to-gliogenic shift in down syndrome human cerebral organoids.Molecular brain · 2026Article
- Altered immune and inflammatory gene expression in prefrontal cortex of antipsychotic-free schizophrenia subjects.Brain, behavior, & immunity - health · 2025Article
- A Novel Frameshift Variant and a PartialGenes · 2025Review
- The restoration of REST inhibits reactivity of Down syndrome iPSC-derived astrocytes.Frontiers in molecular neuroscience · 2025Article
- Chromatin modifiers in neurodevelopment.Frontiers in molecular neuroscience · 2025Review
- Clinical characteristics and genetic analysis of four pediatric patients with Kleefstra syndrome.BMC medical genomics · 2024Article
- Establishment of human pluripotent stem cell-derived cortical neurosphere model to study pathomechanisms and chemical toxicity in Kleefstra syndrome.Scientific reports · 2024Article
- REST in the Road Map of Brain Development.Cellular and molecular neurobiology · 2023Review
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Genetic evidence indicates disrupted epigenetic regulation as a major risk factor for psychiatric disorders, but the molecular mechanisms that drive this association remain to be determined. EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a genetic disorder linked with neurodevelopmental disorders and associated with schizophrenia. Here, we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. We further show that EHMT1 regulates NRSF/REST indirectly via repression of miRNA and leads to aberrant neuronal gene regulation and neurodevelopment timing. Expression of a NRSF/REST mRNA that lacks the miRNA-binding sites restores neuronal gene regulation to EHMT1 deficient cells. Significantly, the EHMT1-regulated miRNA gene set not only controls NRSF/REST but is enriched for association for Intellectual Disability (ID) and schizophrenia. This reveals a broad molecular interaction between H3K9 demethylation, NSRF/REST regulation and risk for ID and Schizophrenia.
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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.