Quantitatively predictable control of Drosophila transcriptional enhancers in vivo with engineered transcription factors
Abstract
Genes are regulated by transcription factors that bind to regions of genomic DNA called enhancers. Considerable effort is focused on identifying transcription factor binding sites, with the goal of predicting gene expression from DNA sequence. Despite this effort, general, predictive models of enhancer function are currently lacking. Here we combine quantitative models of enhancer function with manipulations using engineered transcription factors to examine the extent to which enhancer function can be controlled in a quantitatively predictable manner. Our models, which incorporate few free parameters, can accurately predict the contributions of ectopic transcription factor inputs. These models allow the predictable 'tuning' of enhancers, providing a framework for the quantitative control of enhancers with engineered transcription factors.
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Modelling the effects of targeting engineered transcription activators and repressors to enhancers suggested that transcription factors can contribute additively to enhancer function, regardless of their identity.
“For example, modelling the effects of targeting engineered transcription activators and repressors to enhancers suggested that TFs can contribute additively to enhancer function, regardless of their identity [96].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [96]
Cites
Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq
Treutlein, B., Brownfield, D. G., Wu, A. R., Neff, N. F., Mantalas, G. L., Espinoza, F. H., Desai, T. J., Krasnow, M. A., & Quake, S. R. (2014) · Nature · doi:10.1038/nature13173 · Cited by 1,342 · see citing works
Low Affinity Binding Site Clusters Confer Hox Specificity and Regulatory Robustness
Crocker, J., Abe, N., Rinaldi, L., McGregor, A. P., Frankel, N., Wang, S., Alsawadi, A., Valenti, P., Plaza, S., Payre, F., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.041 · Cited by 363 · see citing works
Self-citationA Transcription Factor Collective Defines Cardiac Cell Fate and Reflects Lineage History
Junion, G., Spivakov, M., Girardot, C., Braun, M., Gustafson, E. H., Birney, E., & Furlong, E. E. M. (2012) · Cell · doi:10.1016/j.cell.2012.01.030 · Cited by 257 · see citing works
The words of the regulatory code are arranged in a variable manner in highly conserved enhancers
Rastegar, S., Hess, I., Dickmeis, T., Nicod, J. C., Ertzer, R., Hadzhiev, Y., Thies, W.-G., Scherer, G., & Strähle, U. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.03.034 · Cited by 56 · cited 2× · see citing works
“These results suggest that enhancers can act as simple input-output devices, integrating total activation and repression across the enhancer, which is consistent with a growing number of studies 9,24,47–51 , 53 .”
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de Almeida, B. P., Reiter, F., Pagani, M., & Stark, A. (2021) · doi:10.1101/2021.10.05.463203 · Cited by 284
de Almeida, B. P., Reiter, F., Pagani, M., & Stark, A. (2022) · Nature Genetics · doi:10.1038/s41588-022-01048-5 · Cited by 283 · see citing works
Is a super-enhancer greater than the sum of its parts?
Dukler, N., Gulko, B., Huang, Y.-F., & Siepel, A. (2017) · Nature Genetics · doi:10.1038/ng.3759 · Cited by 79 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
- Authors
- Crocker, J., Ilsley, G. R., & Stern, D. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Okinawa Institute of Science and Technology Graduate University (JP)
- Corresponding author
- Crocker, Justin
- Ilsley, Garth R
- Venue
- Nature Genetics
- Published
- 2016-02-08
- Volume
- 48
- Issue
- 3
- Pages
- 292-298
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2255694509
- Cited by
- 35
- References
- 4
- Citations by year
- 2026: 1 · 2024: 7 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 1
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- enhancers, Drosophila embryo, transcription factor binding sites, gene expression regulation
- MeSH terms
- Animals, Base Sequence, Binding Sites, DNA-Binding Proteins, Drosophila melanogaster, Enhancer Elements, Genetic, Models, Genetic, Transcription Factors, Gene Expression Regulation, Developmental
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