ArticleNature methods2018
Resolving systematic errors in widely used enhancer activity assays in human cells.
Article in Nature methods, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 236 citations in OpenAlex.
- RNA-independent cis-autoregulatory circuits within bidirectional gene pairs control metabolism.Science advances · 2026Article
- High-throughput functional characterization of enhancers in totipotent-like cells.Nature communications · 2026Article
- Article
- Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026Article
- Using a modular massively parallel reporter assay to discover context-dependent regulatory activity in type 2 diabetes-linked noncoding regions.HGG advances · 2026Article
- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers.bioRxiv : the preprint server for biology · 2026Article
- STARR-CRAAVT: A platform to identify cell type-specific regulatory elements for next-generation gene therapy.iScience · 2026Article
- Enhancer hubs govern chromatin topology and Th17 cell identity.bioRxiv : the preprint server for biology · 2026Article
- When RNA goes off script: ensuring transcript fidelity in transgene expression.The EMBO journal · 2026Review
- Article
- Integrating natural and engineered genetic variations to decode regulatory influence on blood traits.Cell reports · 2026Article
- Epromoters bind key stress-related transcription factors to regulate clusters of stress response genes.The EMBO journal · 2026Article
- Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.Cell reports · 2026Article
- Identification of novel DNA sequence motifs that modulate transcription in T cells.BMC genomics · 2026Article
- Comprehensive Mapping of Functional Enhancers in Chinese Hamster Ovary Cells.Biotechnology and bioengineering · 2026Article
- Predictive design of tissue-specific mammalian enhancers that functionbioRxiv : the preprint server for biology · 2025Article
- SOSHI-seq: a high-throughput screening assay to test the functionality of putative response elements for nuclear hormone receptors.Scientific reports · 2025Article
- Segmentally duplicated regulatory elements undergo human-specific rewiring.bioRxiv : the preprint server for biology · 2025Article
- Discovering the complete enhancer map of human herpesviruses using a natural language processing model.Nature communications · 2025Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The identification of transcriptional enhancers in the human genome is a prime goal in biology. Enhancers are typically predicted via chromatin marks, yet their function is primarily assessed with plasmid-based reporter assays. Here, we show that such assays are rendered unreliable by two previously reported phenomena relating to plasmid transfection into human cells: (i) the bacterial plasmid origin of replication (ORI) functions as a conflicting core promoter and (ii) a type I interferon (IFN-I) response is activated. These cause confounding false positives and negatives in luciferase assays and STARR-seq screens. We overcome both problems by employing the ORI as core promoter and by inhibiting two IFN-I-inducing kinases, enabling genome-wide STARR-seq screens in human cells. In HeLa-S3 cells, we uncover strong enhancers, IFN-I-induced enhancers, and enhancers endogenously silenced at the chromatin level. Our findings apply to all episomal enhancer activity assays in mammalian cells and are key to the characterization of human enhancers.
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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.