In pursuit of design principles of regulatory sequences
Abstract
Instructions for when, where and to what level each gene should be expressed are encoded within regulatory sequences. The importance of motifs recognized by DNA-binding regulators has long been known, but their extensive characterization afforded by recent technologies only partly accounts for how regulatory instructions are encoded in the genome. Here, we review recent advances in our understanding of regulatory sequences that influence transcription and go beyond the description of motifs. We discuss how understanding different aspects of the sequence-encoded regulation can help to unravel the genotype-phenotype relationship, which would lead to a more accurate and mechanistic interpretation of personal genome sequences.
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Measuring enhancer activity of synthetic, systematically designed DNA sequences with TFBSs placed in an otherwise inert sequence context is an alternative way to study the cis-regulatory code.
“An alternative way to study the cis-regulatory code is to measure the enhancer activity of synthetic, systematically designed DNA sequences, where TF binding sites (TFBSs) are placed in an otherwise inert sequence context.27,30,31,32,33,34”
From Design principles of cell-state-specific enhancers in hematopoiesis (2025) · cites this paper as [34]
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- Authors
- Levo, M., & Segal, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Segal, Eran
- Venue
- Nature Reviews Genetics
- Published
- 2014-06-10
- Volume
- 15
- Issue
- 7
- Pages
- 453-468
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2116634411
- Cited by
- 215
- References
- 16
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 18 · 2021: 28 · 2020: 13 · 2019: 19 · 2018: 22 · 2017: 23 · 2016: 27 · 2015: 25 · 2014: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (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 › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- gene regulatory sequences, transcriptional regulation, DNA-binding motifs, transcription factor binding, gene expression patterns, genotype-phenotype correlation
- MeSH terms
- Animals, Base Composition, Base Sequence, Binding Sites, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Molecular Sequence Data, Nucleosomes, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Genome, Genome-Wide Association Study, High-Throughput Screening Assays
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