ArticleNature genetics2023
Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear enhancer gene regulatory activity during cell state transitions.
Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 40 citations in OpenAlex.
- Biomarker discovery and patient stratification in pancreatic cancer using incomplete multi-omics data.PLoS computational biology · 2026Article
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- Towards efficient perturbation for the noncoding genome.Nature communications · 2026Article
- Mapping enhancer-gene regulatory interactions from single-cell data.Nature genetics · 2026Article
- Region-Level Design and Analysis of CRISPR Perturbation Screens with FRACTEL.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- 3D chromatin architecture in cancer: mechanisms of dysregulation and emerging therapeutic strategies.Experimental & molecular medicine · 2026Review
- Massively parallel reporter assay-informed modeling improves prediction of context-specific enhancer-gene regulatory interactions.Nucleic acids research · 2026Article
- Functional chromatin signatures premark future lineage-specific enhancers.Cell genomics · 2026Article
- Intermolecular 3'UTR-3'UTR interactions drive Wnt gene activation through heteromeric protein assembly.bioRxiv : the preprint server for biology · 2026Article
- FourC: identifying significant and differential contacts in 1D chromatin conformation data.bioRxiv : the preprint server for biology · 2026Article
- Predicting neuroblastoma prognosis using machine learning analysis of metabolism-related gene network perturbation.BMC pediatrics · 2026Article
- CRISPR-based Transcriptional Regulation: Technologies, Applications, and Future Directions.DNA · 2025Article
- Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.Nature cell biology · 2025Article
- Aberrant Enhancer Regulation, Phase Separation, and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2025Review
- Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells.Stem cell reports · 2025Article
- High expression ofBiochemistry and biophysics reports · 2025Article
- Deciphering aging-associated prognosis and heterogeneity in gastric cancer through a machine learning-driven approach.iScience · 2025Article
- Non-local modeling of enhancer-promoter interactions, a correspondence on "LOCO-EPI: Leave-one-chromosome-out (LOCO) as a benchmarking paradigm for deep learning based prediction of enhancer-promoter interactions".Applied intelligence (Dordrecht, Netherlands) · 2025Article
- CXCL Gene Clusters Regulated by Enhancer-Mediated DNA Looping Alteration in Pancreatic Cancer Cells.Journal of cellular and molecular medicine · 2025Article
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
Comprehensive enhancer discovery is challenging because most enhancers, especially those contributing to complex diseases, have weak effects on gene expression. Our gene regulatory network modeling identified that nonlinear enhancer gene regulation during cell state transitions can be leveraged to improve the sensitivity of enhancer discovery. Using human embryonic stem cell definitive endoderm differentiation as a dynamic transition system, we conducted a mid-transition CRISPRi-based enhancer screen. We discovered a comprehensive set of enhancers for each of the core endoderm-specifying transcription factors. Many enhancers had strong effects mid-transition but weak effects post-transition, consistent with the nonlinear temporal responses to enhancer perturbation predicted by the modeling. Integrating three-dimensional genomic information, we were able to develop a CTCF-loop-constrained Interaction Activity model that can better predict functional enhancers compared to models that rely on Hi-C-based enhancer-promoter contact frequency. Our study provides generalizable strategies for sensitive and systematic enhancer discovery in both normal and pathological cell state transitions.
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