ArticleNature biotechnology2012
Massively parallel functional dissection of mammalian enhancers in vivo.
Article in Nature biotechnology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 347 papers, 1 of them a synthesis that pooled it.
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Who cites it
347 citing papers in PubMed, 1 synthesis or guideline pooled it, 574 citations in OpenAlex.
- Meta-analysis of massively parallel reporter assays enables prediction of regulatory function across cell types.Human mutation · 2019Pooled it
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Promoter identity shapes splicing outcomes and fidelity.Nature communications · 2026Article
- Opportunities for artificial intelligence and synthetic biology in designing living drug delivery systems.Advanced drug delivery reviews · 2026Review
- Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026Article
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome 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
- Identifying severe COVID-19 risk variants modulating enhancer reporter activity in lung cells.PLoS genetics · 2026Article
- Expression-linked promoter selection (ELiPS) engineers short, strong ubiquitous promoters for gene therapy applications.bioRxiv : the preprint server for biology · 2026Article
- Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers.bioRxiv : the preprint server for biology · 2026Article
- Informational blueprints reveal condition-dependent gene regulatory architectures.bioRxiv : the preprint server for biology · 2026Article
- Massively parallel reporter assays: from barcodes to biology.Nature reviews. Genetics · 2026Article
- Technical and biological sources of noise confound multiplexed enhancer AAV screening.Nature communications · 2026Article
- Retracing and rewriting the evolutionary trajectories of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Predictive modeling of gene expression and localization of DNA binding site using deep convolutional neural networks.PLoS computational biology · 2026Article
- In silico genome transplants and the cis-regulatory basis of biodiversity.Trends in genetics : TIG · 2026Review
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Comprehensive evaluation of diverse massively parallel reporter assays to functionally characterize human enhancers genome-wide.Genome biology · 2025Article
287 more citing papers are in PubMed but not listed here.
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13 authors at 6 institutions in 1 country.
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Abstract
The functional consequences of genetic variation in mammalian regulatory elements are poorly understood. We report the in vivo dissection of three mammalian enhancers at single-nucleotide resolution through a massively parallel reporter assay. For each enhancer, we synthesized a library of >100,000 mutant haplotypes with 2-3% divergence from the wild-type sequence. Each haplotype was linked to a unique sequence tag embedded within a transcriptional cassette. We introduced each enhancer library into mouse liver and measured the relative activities of individual haplotypes en masse by sequencing the transcribed tags. Linear regression analysis yielded highly reproducible estimates of the effect of every possible single-nucleotide change on enhancer activity. The functional consequence of most mutations was modest, with ∼22% affecting activity by >1.2-fold and ∼3% by >2-fold. Several, but not all, positions with higher effects showed evidence for purifying selection, or co-localized with known liver-associated transcription factor binding sites, demonstrating the value of empirical high-resolution functional analysis.
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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.