Cited by 1,125Genomics and Chromatin DynamicsChromatin Remodeling and CancerGene Regulatory Network Analysis

Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq

Arnold, Cosmas D., Gerlach, Daniel, Stelzer, Christoph, Boryń, Łukasz M., Rath, Martina, Stark, Alexander·2013·Science

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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Crossref · 10.1126/science.1232542

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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.”
  • 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]).”

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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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