ArticleCell systems2017
Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers.
Article in Cell systems, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 130 citations in OpenAlex.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer.Genome research · 2026Article
- Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026Article
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer.bioRxiv : the preprint server for biology · 2026Article
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- dHyperCas12a enables multiplexed CRISPRi screens.Nature communications · 2026Article
- Emerging trends in gene and cell therapy: CRISPR in DNA editing and beyond.Cell reports. Medicine · 2026Review
- CRISPR-based Transcriptional Regulation: Technologies, Applications, and Future Directions.DNA · 2025Article
- HyperCas12a enables multiplexed CRISPRi screens.bioRxiv : the preprint server for biology · 2025Article
- Genetic disruption of the baculum compromises the ability of male mice to copulate.PLoS genetics · 2025Article
- Enhancing Specificity, Precision, Accessibility, Flexibility, and Safety to Overcome Traditional CRISPR/Cas Editing Challenges and Shape Future Innovations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts.Genome research · 2025Article
- CRISPR GENome and epigenome engineering improves loss-of-function genetic-screening approaches.Cell reports methods · 2025Article
- Engineering novel CRISPRi repressors for highly efficient mammalian gene regulation.Genome biology · 2025Article
- Auricular malformations are driven by copy number variations in a hierarchical enhancer cluster and a dominant enhancer recapitulates human pathogenesis.Nature communications · 2025Article
- Estrogen-induced chromatin looping changes identify a subset of functional regulatory elements.Genome research · 2025Article
- Active learning of enhancers and silencers in the developing neural retina.Cell systems · 2025Article
- Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook.Frontiers in genetics · 2025Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to affect gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that uses 2 different repressive domains, KRAB and SID, to prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor α binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of different ERBS combinations identified supportive ERBS that contribute only when predominant sites are active. Using mathematical modeling, we find strong evidence for collaboration between predominant and supportive ERBS. Overall, our findings expose a complex functional hierarchy of enhancers, where multiple loci bound by the same transcription factor combine to fine-tune the expression of target genes.
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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.