Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq
Abstract
Genomic enhancers are important regulators of gene expression, but their identification is a challenge, and methods depend on indirect measures of activity. We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.
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Genome-wide 'shotgun MPRAs' avoid a priori assumptions about which sequences to test.
“In contrast with MPRAs relying on re-synthesis of candidate sequences, genome-wide ‘shotgun MPRAs’108,174,183,188 nicely avoid a priori assumptions about which sequences to test.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [174]
Certain promoters, termed epromoters, can also function as enhancers.
“Finally, evidence from multiple sources including reporter assays [169, 175, 239, 240], CRISPR [240–242], chromatin mapping [243, 244] and population genetics analysis [207, 245] suggests that certain promoters, termed ‘epromoters’, can also function as enhancers (reviewed in [246]).”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [169]
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- Authors
- Arnold, C. D., Gerlach, D., Stelzer, C., Boryń, Ł. M., Rath, M., & Stark, A.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Stark, Alexander
- Venue
- Science
- Published
- 2013-03
- Volume
- 339
- Issue
- 6123
- Pages
- 1074-1077
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2077874719
- Cited by
- 1,125
- References
- 48
- Citations by year
- 2026: 74 · 2025: 113 · 2024: 107 · 2023: 99 · 2022: 80 · 2021: 96 · 2020: 106 · 2019: 85 · 2018: 77 · 2017: 75 · 2016: 74 · 2015: 64 · 2014: 53 · 2013: 21
- FWCI
- 31.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- enhancer activity, STARR-seq, Drosophila, cell type-specific enhancers, transcriptional regulation, gene expression regulation, enhancer screen, developmental regulators
- MeSH terms
- Animals, Chromosome Mapping, Drosophila melanogaster, Enhancer Elements, Genetic, Female, Gene Expression Regulation, HeLa Cells, Humans, Ovary, Transcription, Genetic, Genome, Sequence Analysis, DNA, Gene Expression Regulation, Developmental
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