ArticleNature genetics2021
BRD4 orchestrates genome folding to promote neural crest differentiation.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 92 citations in OpenAlex.
- A scaffolding element rewires local 3D chromatin architecture during differentiation.Nature communications · 2026Article
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Genome folding and nuclear speckles converge to orchestrate fibroblast activation.Science advances · 2026Article
- Pioneer transcription factors direct tissue-specific cohesin chromatin entry and three-dimensional genome organization.Nature genetics · 2026Article
- Targeting bromodomain and extraterminal proteins in cardiovascular disease: Pathological mechanisms and therapeutic applications.The Journal of international medical research · 2026Review
- Loop extrusion by cohesin plays a role in enhancer-activated gene expression early in differentiation.Nature communications · 2026Article
- Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich's ataxia.Molecular cell · 2026Article
- Cohesin cofactor dosage sets the rate of loop extrusion, rendering genome folding tunable yet vulnerable to genetic disruption.Molecular cell · 2026Article
- Histo-LCM-Hi-C Reveals 3D Chromatin Conformations of Spatially Localized Rare Cells in Tissues at High Resolution.Genomics, proteomics & bioinformatics · 2026Article
- BRD4 promotes endodermal cell fate during mammalian lung development.JCI insight · 2026Article
- The role of cohesin loading at enhancers in the flux of loop extrusion and long-range transcriptional control.bioRxiv : the preprint server for biology · 2026Article
- A genetic screen for modifiers of cohesin clustering identifies regulators of genome folding.Science advances · 2026Article
- Adam13 interacts with large protein complexes to regulate histone modification and gene expression.Frontiers in cell and developmental biology · 2026Article
- Engineering the Link: From Genome Interaction Maps to Functional Insight.Advanced biology · 2025Review
- CRISPR live-cell imaging reveals chromatin dynamics and enhancer interactions at multiple non-repetitive loci.Nature biotechnology · 2025Article
- Dosage sensitivity of the loop extrusion rate confers tunability to genome folding while creating vulnerability to genetic disruption.bioRxiv : the preprint server for biology · 2025Article
- Nuclear FGF2 orchestrates phase separation-mediated rDNA chromatin architecture to control BMSCs cell fate.Bone research · 2025Article
- BRD4 Mediates Transforming Growth Factor-β-Induced Smooth Muscle Cell Differentiation from Mesenchymal Progenitor Cells.International journal of molecular sciences · 2025Article
- Cohesin Loading Factor NIPBL Is Essential for MYCN Expression and MYCN-Driven Oncogenic Transcription in Neuroblastoma.Cancers · 2025Article
- Jund orchestratesProceedings of the National Academy of Sciences of the United States of America · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Higher-order chromatin structure regulates gene expression, and mutations in proteins mediating genome folding underlie developmental disorders known as cohesinopathies. However, the relationship between three-dimensional genome organization and embryonic development remains unclear. Here we define a role for bromodomain-containing protein 4 (BRD4) in genome folding, and leverage it to understand the importance of genome folding in neural crest progenitor differentiation. Brd4 deletion in neural crest results in cohesinopathy-like phenotypes. BRD4 interacts with NIPBL, a cohesin agonist, and BRD4 depletion or loss of the BRD4-NIPBL interaction reduces NIPBL occupancy, suggesting that BRD4 stabilizes NIPBL on chromatin. Chromatin interaction mapping and imaging experiments demonstrate that BRD4 depletion results in compromised genome folding and loop extrusion. Finally, mutation of individual BRD4 amino acids that mediate an interaction with NIPBL impedes neural crest differentiation into smooth muscle. Remarkably, loss of WAPL, a cohesin antagonist, rescues attenuated smooth muscle differentiation resulting from BRD4 loss. Collectively, our data reveal that BRD4 choreographs genome folding and illustrates the relevance of balancing cohesin activity for progenitor differentiation.
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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.