ArticleGenome biology2025
Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes.
Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed.
- Systematic CRISPRi perturbation of 1,408 autism risk genes maps multilevel transcriptional convergence in human cortical neurons.bioRxiv : the preprint server for biology · 2026Article
- Protocol to identify genes required for cardiomyocyte development using Perturb-Seq.STAR protocols · 2026Article
- Region-Level Design and Analysis of CRISPR Perturbation Screens with FRACTEL.bioRxiv : the preprint server for biology · 2026Article
- Subtype-specific enhancer RNAs define transcriptional regulators and prognosis in breast cancers.Molecular oncology · 2026Article
- Perturbation of genes linked to common schizophrenia risk variants identifies cilia programs.bioRxiv : the preprint server for biology · 2026Article
- Reprogramming of neuronal genome function and phenotype by astrocytes.bioRxiv : the preprint server for biology · 2026Article
- Comprehensive perturbation of transcription factors in human cardiomyocytes reveals the regulatory architecture of congenital heart disease.bioRxiv : the preprint server for biology · 2026Article
- Mapping Non-Coding Epimutations in Breast Cancer: Advancing Epigenetics Towards Precision Medicine.Sub-cellular biochemistry · 2026Review
- Benchmarking and optimizing Perturb-seq in differentiating human pluripotent stem cells.Stem cell reports · 2025Article
- IgRENE: integrating gene regulatory networks and drug ontologies towards selected modification of target gene's expression.Briefings in bioinformatics · 2025Article
- GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.Genome biology · 2025Article
- Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Identification and functional analysis ofTranslational cancer research · 2025Article
- GWAS-Informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.bioRxiv : the preprint server for biology · 2024Article
- Towards functional maps of non-coding variants in cancer.Frontiers in genome editing · 2024Review
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Abstract
backgroundGenetic studies have associated thousands of enhancers with breast cancer (BC). However, the vast majority have not been functionally characterized. Thus, it remains unclear how BC-associated enhancers contribute to cancer.
resultsHere, we perform single-cell CRISPRi screens of 3513 regulatory elements associated with breast cancer to measure the impact of these regions on transcriptional phenotypes. Analysis of > 500,000 single-cell transcriptomes in two breast cancer cell lines shows that perturbation of BC-associated enhancers disrupts breast cancer gene programs. We observe BC-associated enhancers that directly or indirectly regulate the expression of cancer genes. We also find one-to-multiple and multiple-to-one network motifs where enhancers indirectly regulate cancer genes. Notably, multiple BC-associated enhancers indirectly regulate TP53. Comparative studies illustrate subtype specific functions between enhancers in ER + and ER - cells. Finally, we develop the pySpade package to facilitate analysis of single-cell enhancer screens.
conclusionsOverall, we demonstrate that enhancers form regulatory networks that link cancer genes in the genome, providing a more comprehensive understanding of the contribution of enhancers to breast cancer development.
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