The DOI matches its Crossref record; 101 of the 101 references it cites were found in a registry or an index.
Systematic dissection of genomic features determining transcription factor binding and enhancer function
Open accessAbstract
Significance: A central question in biology is how transcription factors (TFs) recognize specific binding sites in enhancers and regulate gene expression. In general, only a fraction of potential binding sites for TFs are occupied in a particular cell type. TF affinity for a motif site, local interactions among TFs, and larger-scale chromatin accessibility can influence binding, although the relative contributions of these factors is unclear. Moreover, little is known about how specific combinations of TFs control quantitative gene expression once bound. Here, we use large-scale synthetic biology approaches to explore the features that govern TF binding vs. enhancer activity. This approach provides a paradigm for systematic study of key regulatory sequences within enhancers and how they interact to influence gene expression.
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“A major advantage of MPRAs is that sequences to be tested can simply be synthesized, enabling straightforward saturation mutagenesis [G] of enhancers67,184,185 as well as programming synthetic enhancers to inform modelling of their properties186,187.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [186]
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Self-citationFIMO: scanning for occurrences of a given motif
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Determinants of enhancer and promoter activities of regulatory elements
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Linear models enable powerful differential activity analysis in massively parallel reporter assays
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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
Transcription factors: Bridge between cell signaling and gene regulation
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DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of enhancers
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Metadata
- Authors
- Grossman, S. R., Zhang, X., Wang, L., Engreitz, J., Melnikov, A., Rogov, P., Tewhey, R., Isakova, A., Deplancke, B., Bernstein, B. E., Mikkelsen, T. S., & Lander, E. S.
- Affiliations
- Broad Institute (US)
- SIB Swiss Institute of Bioinformatics (CH)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-01-30
- Volume
- 114
- Issue
- 7
- Pages
- E1291-E1300
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5321001
- OpenAlex
- W2581468399
- Cited by
- 165
- References
- 101
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 9 · 2023: 14 · 2022: 20 · 2021: 21 · 2020: 23 · 2019: 20 · 2018: 18 · 2017: 10
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- HHS | NIH | National Human Genome Research Institute (2U54HG003067-10)
- HHS | NIH | National Institute of General Medical Sciences (T32GM007753)
- Office of Extramural Research, National Institutes of Health (R01 HG006785)
- 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 › Peroxisome Proliferator-Activated Receptors
- Keywords
- enhancer function, transcription factor binding, PPARγ, transcription factor interaction, chromatin accessibility, binding site affinity, massively parallel reporter assay, synthetic enhancers, adipogenesis, gene expression regulation, human genetic variation
- MeSH terms
- Animals, Binding Sites, Enhancer Elements, Genetic, Gene Expression Regulation, Mutation, Protein Binding, Transcription Factors, Genomics, 3T3-L1 Cells, PPAR gamma, Mice, Nucleotide Motifs
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