ArticleeLife2021
How subtle changes in 3D structure can create large changes in transcription.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed.
- Stable epigenetic states set single-cell activation thresholds in mammalian expression systems.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- Enhancer control of promoter activity and variability via frequency modulation of clustered transcriptional bursts.Nature genetics · 2026Article
- Genome-wide absolute quantification of chromatin looping.Nature structural & molecular biology · 2026Article
- Live-cell imaging of enhancer-promoter dynamics reveals transient contact-driven gene activation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Cohesin bridging as a physical principle of enhancer-promoter communication.bioRxiv : the preprint server for biology · 2026Article
- De novo formation of cis-regulatory contacts in the absence of NIPBL-driven chromatin loop extrusion.Nature genetics · 2026Article
- Loop Extrusion Accelerates Long-Range Enhancer-Promoter Searches in Living Embryos.bioRxiv : the preprint server for biology · 2026Article
- Hierarchical Chromatin Rewiring Orchestrates Early Transcriptional Regulation in Mouse Cerebral Cortex Following Focal Ischemia.bioRxiv : the preprint server for biology · 2026Article
- Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding.Nature genetics · 2026Article
- ChromNet: A Multi-Task Learning Framework for Cross-Cell Type Prediction of 3D Chromatin Interactions Using Epigenetic Signals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 3D genome folding in epigenetic regulation and cellular memory.Trends in cell biology · 2026Review
- Uniform dynamics of cohesin-mediated loop extrusion in living human cells.Nature genetics · 2025Article
- Nanoscale dynamics of enhancer-promoter interactions during exit from pluripotency.Nucleic acids research · 2025Article
- Molecular and developmental deficits in Smith-Magenis syndrome human stem cell-derived cortical neural models.American journal of human genetics · 2025Article
- RETRACTED: Kinetic organization of the genome revealed by ultraresolution multiscale live imaging.Science (New York, N.Y.) · 2025Article
- Transcriptional programs of cell identity and p53-induced stress responses are associated with distinctive features of spatial genome organization.Nucleic acids research · 2025Article
- CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation.Nature structural & molecular biology · 2025Article
- Non-disruptive 3D profiling of combinations of epigenetic marks in single cells.bioRxiv : the preprint server for biology · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Animal genomes are organized into topologically associated domains (TADs). TADs are thought to contribute to gene regulation by facilitating enhancer-promoter (E-P) contacts within a TAD and preventing these contacts across TAD borders. However, the absolute difference in contact frequency across TAD boundaries is usually less than 2-fold, even though disruptions of TAD borders can change gene expression by 10-fold. Existing models fail to explain this hypersensitive response. Here, we propose a futile cycle model of enhancer-mediated regulation that can exhibit hypersensitivity through bistability and hysteresis. Consistent with recent experiments, this regulation does not exhibit strong correlation between E-P contact and promoter activity, even though regulation occurs through contact. Through mathematical analysis and stochastic simulation, we show that this system can create an illusion of E-P biochemical specificity and explain the importance of weak TAD boundaries. It also offers a mechanism to reconcile apparently contradictory results from recent global TAD disruption with local TAD boundary deletion experiments. Together, these analyses advance our understanding of cis-regulatory contacts in controlling gene expression and suggest new experimental directions.
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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.