ArticleMolecular cell2020
Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 85 citations in OpenAlex.
- Stem cell derived neural organoid approaches for neurological diseases.Neural regeneration research · 2026Article
- MECP2Science China. Life sciences · 2026Article
- Brain organoids and genome editing: A new era in understanding human brain development and disorders.Neural regeneration research · 2026Article
- Neural peer pressure: intercellular dynamics and emergent phenotypes in the mosaic Rett syndrome brain.Cell communication and signaling : CCS · 2026Review
- Multi-omics characterization of developing forebrain organoids unravels the dynamic molecular events of Rett syndrome pathogenesis.Journal of neurodevelopmental disorders · 2026Article
- Cocaine-Induced Changes in the BRD4 Interactome Identifies Casein Kinase 1 Epsilon as a Therapeutic Target.Journal of neurochemistry · 2026Article
- Histone acetylation and methylation in rare diseases: from molecular mechanisms to clinical presentations.Frontiers in cell and developmental biology · 2026Review
- Pluripotent stem cells-based neural organoids for modelling human brain development and diseases.Cell & bioscience · 2025Review
- Radiofrequency regulates the BET-mediated pathways in radial glia differentiation in human cortical development.Cell reports · 2025Article
- Functional Validation of Alcohol Dependence-AssociatedInternational journal of stem cells · 2025Article
- Exploring the complexity of MECP2 function in Rett syndrome.Nature reviews. Neuroscience · 2025Review
- Global analysis of excitotoxicity-induced alterations in RNA structure and RNA-protein binding in neurons.iScience · 2025Article
- Phase Separation in Chromatin Organization and Human Diseases.International journal of molecular sciences · 2025Review
- Article
- Modelling human brain development and disease with organoids.Nature reviews. Molecular cell biology · 2025Review
- A Blueprint for Translational Precision Medicine in Autism Spectrum Disorder and Related Neurogenetic Syndromes.Journal of child and adolescent psychopharmacology · 2025Review
- Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome.Scientific reports · 2025Article
- The chromatin tapestry as a framework for neurodevelopment.Genome research · 2024Review
- Involvement of extracellular vesicle microRNA clusters in developing healthy and Rett syndrome brain organoids.Cellular and molecular life sciences : CMLS · 2024Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Rett syndrome (RTT), mainly caused by mutations in methyl-CpG binding protein 2 (MeCP2), is one of the most prevalent intellectual disorders without effective therapies. Here, we used 2D and 3D human brain cultures to investigate MeCP2 function. We found that MeCP2 mutations cause severe abnormalities in human interneurons (INs). Surprisingly, treatment with a BET inhibitor, JQ1, rescued the molecular and functional phenotypes of MeCP2 mutant INs. We uncovered that abnormal increases in chromatin binding of BRD4 and enhancer-promoter interactions underlie the abnormal transcription in MeCP2 mutant INs, which were recovered to normal levels by JQ1. We revealed cell-type-specific transcriptome impairment in MeCP2 mutant region-specific human brain organoids that were rescued by JQ1. Finally, JQ1 ameliorated RTT-like phenotypes in mice. These data demonstrate that BRD4 dysregulation is a critical driver for RTT etiology and suggest that targeting BRD4 could be a potential therapeutic opportunity for RTT.
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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.