ArticleCell genomics2025
Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations.
Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Transcription and Three-Dimensional Genome Organization: Cause, Consequence, or Coordination?BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- Nonlinearities and Switch-Like Behavior in Gene Expression: From Genetics to Biochemistry and Back.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Cohesin acts as a transcriptional gatekeeper by restraining pause-release to promote processive elongation.Nature communications · 2026Article
- Genome folding and nuclear speckles converge to orchestrate fibroblast activation.Science advances · 2026Article
- Master Regulator SMC1A, Stabilized by N6-Methyladenosine Reader IGF2BP1, Promotes HCC Progression Through Facilitating Enhancer-Promoter Interaction of Nestin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Non-canonical subunit functions in multiprotein complexes: insights from the Mediator complex.Biochemical Society transactions · 2026Review
- Super Enhancer RNAs Rewrite the Molecular Script of Complex Gene Regulation in the MDD Brain.Communications biology · 2026Article
- Cohesin bridging as a physical principle of enhancer-promoter communication.bioRxiv : the preprint server for biology · 2026Article
- Loop Extrusion Accelerates Long-Range Enhancer-Promoter Searches in Living Embryos.bioRxiv : the preprint server for biology · 2026Article
- Recruitment of transcriptional effectors by Cas9 createsiScience · 2026Article
- Characterization of induced cohesin loop extrusion trajectories in living cells.Nature genetics · 2025Article
- Cohesin regulation of genome organization in mature granule neurons in the mouse cerebellum.Epigenetics & chromatin · 2025Article
- RETRACTED: Kinetic organization of the genome revealed by ultraresolution multiscale live imaging.Science (New York, N.Y.) · 2025Article
- Cohesin in 3D: development, differentiation, and disease.Genes & development · 2025Review
- Distance matters: How protein regulators facilitate enhancer-promoter interactions and transcription.Cell genomics · 2025Article
- Two unrelated distal genes activated by a shared enhancer benefit from localizing inside the same small topological domain.Genes & development · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also most sensitive to perturbations of other regulatory proteins and to BET inhibitor JQ1, this being more a consequence of their distinct enhancer features than distance. Our work predicts that lengthening of intervening sequences can help limit the expression of target genes to specialized cells with optimal trans-factor environments.
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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.