The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
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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Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013) · Nature Methods · doi:10.1038/nmeth.2688 · Cited by 6,422
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013
Heintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., et al. (2007) · Nature Genetics · doi:10.1038/ng1966 · Cited by 3,398 · cited 1×
“Enhancers that associate with active marks and transcription factors are located in open chromatin [17, 19].”
BackgroundThe NHGRI GWAS Catalog, a curated resource of SNP-trait associations
Welter, D., MacArthur, J., Morales, J., Burdett, T., Hall, P., Junkins, H., Klemm, A., Flicek, P., Manolio, T., Hindorff, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1229 · Cited by 2,707
The accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679
An atlas of active enhancers across human cell types and tissues
The FANTOM Consortium, Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., et al. (2014) · Nature · doi:10.1038/nature12787 · Cited by 2,550
Histone modifications at human enhancers reflect global cell-type-specific gene expression
Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450
A unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233
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GeneHancer: genome-wide integration of enhancers and target genes in GeneCards
Fishilevich, S., Nudel, R., Rappaport, N., Hadar, R., Plaschkes, I., Stein, T. I., Rosen, N., Kohn, A., Twik, M., Safran, M., et al. (2017) · Database · doi:10.1093/database/bax028 · Cited by 1,270
The Post-GWAS Era: From Association to Function
Gallagher, M. D., & Chen-Plotkin, A. S. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.04.002 · Cited by 822
Towards a comprehensive catalogue of validated and target-linked human enhancers
Gasperini, M., Tome, J. M., & Shendure, J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0209-0 · Cited by 396
Variant interpretation: functional assays to the rescue
Starita, L. M., Ahituv, N., Dunham, M. J., Kitzman, J. O., Roth, F. P., Seelig, G., Shendure, J., & Fowler, D. M. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.07.014 · Cited by 381
Self-citationCis-regulatory sequences in plants: Their importance, discovery, and future challenges
Schmitz, R. J., Grotewold, E., & Stam, M. E. (2021) · The Plant Cell · doi:10.1093/plcell/koab281 · Cited by 372
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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