Functional footprinting of regulatory DNA
Open accessAbstract
Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution. We demonstrate the approach on a human erythroid enhancer, revealing single TF recognition sites that gate the majority of downstream regulatory function.
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A TALEN-mediated indel scan of the same BCL11A enhancer found the same GATA1 motif.
“A transcription-activator-like effector nuclease (TALEN)-mediated indel scan of the same enhancer found the same motif, albeit via a much lower throughput experiment198.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [198]
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- Authors
- Vierstra, J., Reik, A., Chang, K.-H., Stehling-Sun, S., Zhou, Y., Hinkley, S. J., Paschon, D. E., Zhang, L., Psatha, N., Bendana, Y. R., O'Neil, C. M., Song, A. H., Mich, A. K., Liu, P.-Q., Lee, G., Bauer, D. E., Holmes, M. C., Orkin, S. H., Papayannopoulou, T., Stamatoyannopoulos, G., Rebar, E. J., Gregory, P. D., Urnov, F. D., & Stamatoyannopoulos, J. A.
- Affiliations
- University of Washington (US)
- Sangamo BioSciences (United States) (US)
- Boston Children's Hospital (US)
- Corresponding author
- Urnov, Fyodor D
- Stamatoyannopoulos, John A
- ORCID
- Venue
- Nature Methods
- Published
- 2015-08-31
- Volume
- 12
- Issue
- 10
- Pages
- 927-930
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC5381659
- OpenAlex
- W1721542075
- Cited by
- 133
- References
- 22
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 3 · 2022: 9 · 2021: 12 · 2020: 8 · 2019: 17 · 2018: 21 · 2017: 18 · 2016: 24 · 2015: 5
- FWCI
- 8.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL053750)
- National Human Genome Research Institute (U54HG007010)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK101328, R01DK045365)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- regulatory DNA, DNA double-strand break repair, error-prone repair, transcription factor binding sites
- MeSH terms
- Base Sequence, Binding Sites, Carrier Proteins, DNA Repair, Enhancer Elements, Genetic, Erythrocytes, Erythropoiesis, Humans, Mutation, Nuclear Proteins, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Transcription Factors, Genome, Human, DNA Footprinting, Genomics, DNA Breaks, Double-Stranded
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