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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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“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]
In the citing paper
“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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Cites
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Mapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes
Brand, A. H., & Perrimon, N. (1993) · Development · doi:10.1242/dev.118.2.401 · Cited by 9,510
Tandem repeats finder: a program to analyze DNA sequences
Benson, G. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.2.573 · Cited by 9,374
The Genome Sequence of Drosophila melanogaster
Adams, M. D., Celniker, S., Holt, R. A., Evans, C. A., Gocayne, J. D., Amanatides, P. G., Scherer, S. E., Li, P. W., Hoskins, R. A., Galle, R. F., et al. (2000) · Science · doi:10.1126/science.287.5461.2185 · Cited by 5,902
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
miRBase: integrating microRNA annotation and deep-sequencing data
Kozomara, A., & Griffiths-Jones, S. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq1027 · Cited by 3,634
Repbase Update, a database of eukaryotic repetitive elements
Jurka, J., Kapitonov, V. V., Pavlíček, A., Klonowski, P., Kohany, O., & Walichiewicz, J. (2005) · Cytogenetic and Genome Research · doi:10.1159/000084979 · Cited by 3,413
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
Genome-Wide Mapping of in Vivo Protein-DNA Interactions
Johnson, D. S., Mortazavi, A., Myers, R. M., & Wold, B. (2007) · Science · doi:10.1126/science.1141319 · Cited by 2,927
Polycomb complexes repress developmental regulators in murine embryonic stem cells
Boyer, L. A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L. A., Lee, T. I., Levine, S. S., Wernig, M., Tajonar, A., Ray, M. K., et al. (2006) · Nature · doi:10.1038/nature04733 · Cited by 2,568
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
Self-citationThe UCSC Table Browser data retrieval tool
Karolchik, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh103 · Cited by 2,314
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
Expression of a β-globin gene is enhanced by remote SV40 DNA sequences
Banerji, J., Rusconi, S., & Schaffner, W. (1981) · Cell · doi:10.1016/0092-8674(81)90413-x · Cited by 1,724
ChIP-seq accurately predicts tissue-specific activity of enhancers
Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., et al. (2009) · Nature · doi:10.1038/nature07730 · Cited by 1,639
Using FlyAtlas to identify better Drosophila melanogaster models of human disease
Chintapalli, V. R., Wang, J., & Dow, J. A. T. (2007) · Nature Genetics · doi:10.1038/ng2049 · Cited by 1,479
Robertson, G., Hirst, M., Bainbridge, M., Bilenky, M., Zhao, Y., Zeng, T., Euskirchen, G., Bernier, B., Varhol, R., Delaney, A., et al. (2007) · Nature Methods · doi:10.1038/nmeth1068 · Cited by 1,454
High-Resolution Mapping and Characterization of Open Chromatin across the Genome
Boyle, A. P., Davis, S., Shulha, H. P., Meltzer, P., Margulies, E. H., Weng, Z., Furey, T. S., & Crawford, G. E. (2008) · Cell · doi:10.1016/j.cell.2007.12.014 · Cited by 1,415
Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE
Roy, S., Ernst, J., Kharchenko, P. V., Kheradpour, P., Nègre, N., Eaton, M. L., Landolin, J. M., Bristow, C. A., Ma, L., Lin, M. F., et al. (2010) · Science · doi:10.1126/science.1198374 · Cited by 1,242
Tools for neuroanatomy and neurogenetics in Drosophila
Pfeiffer, B. D., Jenett, A., Hammonds, A. S., Ngo, T.-T. B., Misra, S., Murphy, C., Scully, A. L., Carlson, J. W., Wan, K. H., Laverty, T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803697105 · Cited by 996
Comprehensive analysis of the chromatin landscape in Drosophila melanogaster
Kharchenko, P. V., Alekseyenko, A. A., Schwartz, Y. B., Minoda, A., Riddle, N. C., Ernst, J., Sabo, P. J., Larschan, E., Gorchakov, A. A., Gu, T., et al. (2010) · Nature · doi:10.1038/nature09725 · Cited by 893
Melnikov, A., Murugan, A., Zhang, X., Tesileanu, T., Wang, L., Rogov, P., Feizi, S., Gnirke, A., Callan, C. G., Kinney, J. B., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2137 · Cited by 711
Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures
Stark, A., Lin, M. F., Kheradpour, P., Pedersen, J. S., Parts, L., Carlson, J. W., Crosby, M. A., Rasmussen, M. D., Roy, S., Deoras, A. N., et al. (2007) · Nature · doi:10.1038/nature06340 · Cited by 640
Self-citationRuby, J. G., Stark, E., Johnston, W. K., Kellis, M., Bartel, D. P., & Lai, E. C. (2007) · Genome Research · doi:10.1101/gr.6597907 · Cited by 602
Self-citationA map of open chromatin in human pancreatic islets
Gaulton, K. J., Nammo, T., Pasquali, L., Simon, J. M., Giresi, P. G., Fogarty, M. P., Panhuis, T. M., Mieczkowski, P. A., Secchi, A., Bosco, D., et al. (2010) · Nature Genetics · doi:10.1038/ng.530 · Cited by 540
Massively parallel functional dissection of mammalian enhancers in vivo
Patwardhan, R. P., Hiatt, J. B., Witten, D. M., Kim, M. J., Smith, R. P., May, D., Lee, C., Andrie, J. M., Lee, S.-I., Cooper, G. M., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2136 · Cited by 536
Phenotypic robustness conferred by apparently redundant transcriptional enhancers
Frankel, N., Davis, G. K., Vargas, D., Wang, S., Payre, F., & Stern, D. L. (2010) · Nature · doi:10.1038/nature09158 · Cited by 510
Bonn, S., Zinzen, R. P., Girardot, C., Gustafson, E. H., Perez-Gonzalez, A., Delhomme, N., Ghavi-Helm, Y., Wilczyński, B., Riddell, A., & Furlong, E. E. M. (2012) · Nature Genetics · doi:10.1038/ng.1064 · Cited by 502
High-Throughput Illumina Strand-Specific RNA Sequencing Library PreparationPreprint
Zhong, S., Joung, J., Zheng, Y., Chen, Y.-R., Liu, B., Shao, Y., Xiang, J., Fei, Z., & Giovannoni, J. J. (2011) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot5652 · Cited by 471
Transcriptional Enhancers in Animal Development and Evolution
Levine, M. (2010) · Current Biology · doi:10.1016/j.cub.2010.06.070 · Cited by 465
A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila
Saito, K., Inagaki, S., Mitsuyama, T., Kawamura, Y., Ono, Y., Sakota, E., Kotani, H., Asai, K., Siomi, H., & Siomi, M. C. (2009) · Nature · doi:10.1038/nature08501 · Cited by 440
FlyBase 101 - the basics of navigating FlyBase
McQuilton, P., Pierre, S. E. S., & Thurmond, J. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1030 · Cited by 364
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Nègre, N., Brown, C. D., Shah, P. K., Kheradpour, P., Morrison, C. A., Henikoff, J. G., Feng, X., Ahmad, K., Russell, S. R. H., White, R. A., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000814 · Cited by 341
Defining the Status of RNA Polymerase at Promoters
Core, L. J., Waterfall, J. J., Gilchrist, D. A., Fargo, D. C., Kwak, H., Adelman, K., & Lis, J. T. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.08.034 · Cited by 252
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Perry, M. W., Boettiger, A. N., & Levine, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109873108 · Cited by 228
Rational design of a super core promoter that enhances gene expression
Juven-Gershon, T., Cheng, S., & Kadonaga, J. T. (2006) · Nature Methods · doi:10.1038/nmeth937 · Cited by 223
Kvon, E. Z., Stampfel, G., Yáñez-Cuna, J. O., Dickson, B. J., & Stark, A. (2012) · Genes & Development · doi:10.1101/gad.188052.112 · Cited by 151
Self-citationHe, Q., Bardet, A. F., Patton, B., Purvis, J., Johnston, J. J., Paulson, A., Gogol, M., Stark, A., & Zeitlinger, J. (2011) · Nature Genetics · doi:10.1038/ng.808 · Cited by 128
Self-citationDeciphering the transcriptional cis-regulatory code
Yáñez-Cuna, J. O., Kvon, E. Z., & Stark, A. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.09.007 · Cited by 126
Self-citationParry, T. J., Theisen, J. W. M., Hsu, J.-Y., Wang, Y., Corcoran, D. L., Eustice, M., Ohler, U., & Kadonaga, J. T. (2010) · Genes & Development · doi:10.1101/gad.1951110 · Cited by 121
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Bardet, A. F., He, Q., Zeitlinger, J., & Stark, A. (2011) · Nature Protocols · doi:10.1038/nprot.2011.420 · Cited by 118
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Baxter-Gabbard, K. L. (1972) · FEBS Letters · doi:10.1016/0014-5793(72)80031-0 · Cited by 100
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Cappabianca, L. A., Thomassin, H., PICTET, R. L., & Grange, T. (2003) · Humana Press eBooks · doi:10.1385/1-59259-681-9:427 · Cited by 14
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Ramírez, F., Bhardwaj, V., Arrigoni, L., Lam, K. C., Grüning, B. A., Villaveces, J. M., Habermann, B. H., Akhtar, A., & Manke, T. (2018) · Nature Communications · doi:10.1038/s41467-017-02525-w · Cited by 993
New developments on the Encyclopedia of DNA Elements (ENCODE) data portal
Luo, Y., Hitz, B. C., Gabdank, I., Hilton, J. A., Kagda, M. S., Lam, B. R., Myers, Z., Sud, P., Jou, J., Lin, K. Z., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1062 · Cited by 982
Metadata
- 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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