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Decoding enhancers using massively parallel reporter assays
Open accessAbstract
Enhancers control the timing, location and expression levels of their target genes. Nucleotide variation in enhancers has been shown to lead to numerous phenotypes, including human disease. While putative enhancer sequences and nucleotide variation within them can now be detected in a rapid manner using various genomic technologies, the understanding of the functional consequences of these variants still remains largely unknown. Massively parallel reporter assays (MPRAs) can overcome this hurdle by providing the ability to test thousands of sequences and nucleotide variants within them for enhancer activity en masse. Here, we describe this technology and specifically focus on how it is being used to obtain an increased understanding of enhancer regulatory code and grammar.
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“To this point, new methods have recently emerged that overcome many of the key limitations of earlier technologies. These include single-cell (‘sc’) methods to identify cell-type-specific open chromatin in complex tissues82,83; higher resolution chromosome conformation capture [G] methods to more finely map enhancer–promoter contacts84; MPRAs to dissect or trap enhancer activity on a reporter”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [85]
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Metadata
- Authors
- Inoue, F., & Ahituv, N.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Ahituv, Nadav
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 106
- Issue
- 3
- Pages
- 159-164
- ISSN
- 0888-7543 (ISSN-L)
- PMC
- PMC4540663
- OpenAlex
- W655820313
- Cited by
- 272
- References
- 50
- Citations by year
- 2026: 26 · 2025: 36 · 2024: 25 · 2023: 28 · 2022: 29 · 2021: 36 · 2020: 30 · 2019: 25 · 2018: 11 · 2017: 20 · 2016: 5
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Human Genome Research Institute (1R01HG006768)
- National Cancer Institute (1R01CA197139)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- enhancers, massively parallel reporter assay, enhancer activity, nucleotide variants, regulatory codes, enhancer function, gene expression regulation, variant effect prediction
- MeSH terms
- Binding Sites, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Transcription Factors, Sequence Analysis, DNA, Genomics, High-Throughput Nucleotide Sequencing
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