ArticleScience (New York, N.Y.)2022
Nested epistasis enhancer networks for robust genome regulation.
Article in Science (New York, N.Y.), 2022. 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.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Testing for Genetic Interactions in Complex Disease With Distance Correlation.Biometrical journal. Biometrische Zeitschrift · 2026Article
- Foundation model reveals the shared organization of transcription and topologically associating domains.Cell systems · 2026Article
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- Article
- CRISPR-Cas-based live cell imaging of genome dynamics.Nature reviews. Genetics · 2026Review
- Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026Article
- Region-Level Design and Analysis of CRISPR Perturbation Screens with FRACTEL.bioRxiv : the preprint server for biology · 2026Article
- MINTsC learns multi-way chromatin interactions from single cell high throughput chromatin conformation data.Nature communications · 2026Article
- Rewriting the epigenome: CRISPR tools for biological discovery and therapeutics.Current opinion in biomedical engineering · 2026Article
- CoCUT&Tag maps linked chromatin states at single-molecule, single-cell resolution.bioRxiv : the preprint server for biology · 2026Article
- MINTsC learns multi-way chromatin interactions from single cell high throughput chromatin conformation data.bioRxiv : the preprint server for biology · 2026Article
- CRISPR tiling deletion screens reveal functional enhancers and allelic compensation effects (ACE) on SIN3A transcription.Nature communications · 2026Article
- Boolean logic links chromatin accessibility states to gene expression variability across cell types.Nucleic acids research · 2026Article
- A robust cis-regulatory network ensures Otx2 expression during retinal development.Development (Cambridge, England) · 2026Article
- dHyperCas12a enables multiplexed CRISPRi screens.Nature communications · 2026Article
- Review
- Remodeling ofScience advances · 2026Article
- Rapid promoter evolution of male accessory gland genes is accompanied by divergent expression in closely related Drosophila species.Genetics · 2025Article
21 more citing papers are in PubMed but not listed here.
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17 authors.
Funding
Abstract
Mammalian genomes have multiple enhancers spanning an ultralong distance (>megabases) to modulate important genes, but it is unclear how these enhancers coordinate to achieve this task. We combine multiplexed CRISPRi screening with machine learning to define quantitative enhancer-enhancer interactions. We find that the ultralong distance enhancer network has a nested multilayer architecture that confers functional robustness of gene expression. Experimental characterization reveals that enhancer epistasis is maintained by three-dimensional chromosomal interactions and BRD4 condensation. Machine learning prediction of synergistic enhancers provides an effective strategy to identify noncoding variant pairs associated with pathogenic genes in diseases beyond genome-wide association studies analysis. Our work unveils nested epistasis enhancer networks, which can better explain enhancer functions within cells and in diseases.
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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.