High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq
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Cell-type specific regulation of gene expression requires the activation of promoters by distal genomic elements defined as enhancers. The identification and the characterization of enhancers are challenging in mammals due to their genome complexity. Here we develop CapStarr-Seq, a novel high-throughput strategy to quantitatively assess enhancer activity in mammals. This approach couples capture of regions of interest to previously developed Starr-seq technique. Extensive assessment of CapStarr-seq demonstrates accurate quantification of enhancer activity. Furthermore, we find that enhancer strength is associated with binding complexity of tissue-specific transcription factors and super-enhancers, while additive enhancer activity isolates key genes involved in cell identity and function. The CapStarr-Seq thus provides a fast and cost-effective approach to assess the activity of potential enhancers for a given cell type and will be helpful in decrypting transcription regulation mechanisms. Characterizing mammalian gene expression regulation by enhancer elements is complicated by the size and complexity of the genome. Here Vanhille et al.demonstrate CapStarr-Seq, a novel high-throughput method for assessing potential enhancers and deciphering the mechanisms regulating transcription
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MPRAs have been applied to assess biochemically annotated candidate enhancers, candidate enhancers harbouring variants that potentially mediate eQTLs, and even scans of the entire human genome.
“MPRAs have been applied to assess biochemically annotated candidate enhancers77,176-178, candidate enhancers harbouring variants that potentially mediate eQTLs179-182, and even scans of the entire human genome108,183.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [177]
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- Authors
- Vanhille, L., Griffon, A., Maqbool, M. A., Zacarias-Cabeza, J., Dao, L. T. M., Fernandez, N., Ballester, B., Andrau, J. C., & Spicuglia, S.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Spicuglia, Salvatore
- ORCID
- Venue
- Nature Communications
- Published
- 2015-04-15
- Volume
- 6
- Issue
- 1
- Pages
- 6905-6905
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2091688007
- Cited by
- 158
- References
- 9
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 5 · 2023: 14 · 2022: 17 · 2021: 18 · 2020: 22 · 2019: 19 · 2018: 16 · 2017: 14 · 2016: 8 · 2015: 11
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- HAL AMU (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Aix-Marseille Université (ANR 11-IDEX-0001-02)
- Infrastructures en Biologie Santé et Agronomie
- European Commission (262055, 282510, 2007–2013, FP7 2007-2013, FP7/2007)
- Science Foundation Ireland
- Agence Nationale de la Recherche (ANR-11-IDEX-0001, ANR11IDEX000102, ANR-10-INBS-0009, ANR- 10-INBS-09, ANR-11-IDEX, ANR-10, IDEX-0001-02, 10-INBS-09)
- Institut National de la Santé et de la Recherche Médicale (ANR-11-IDEX-0001-02)
- 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 › Epigenetics and DNA Methylation
- Keywords
- enhancer activity, transcriptional regulation, super-enhancers, tissue-specific transcription factors, cell identity genes, cell type-specific gene expression, mammalian gene regulation
- MeSH terms
- Animals, Enhancer Elements, Genetic, Gene Expression Regulation, Male, Promoter Regions, Genetic, Transcription Factors, Gene Expression, Sequence Analysis, DNA, NIH 3T3 Cells, Chromatin Immunoprecipitation, Mice, High-Throughput Nucleotide Sequencing
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