Suboptimization of developmental enhancers
Open accessAbstract
For gene enhancers, less is more: Weak enhancer sequences provide just the right amount of gene activity. Farley et al. systematically examined millions of synthetic variants of the Otx enhancer, a motif needed for gene expression in the nervous system of the sea squirt Ciona. Proper gene activity resulted when there were imperfect matches to the motif showing strongest enhancer binding and gene activation. When “optimal” motifs were incorporated, ectopic expression ensued, with aberrant gene activation outside the nervous system. Science , this issue p. 325
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Flexible enhancer grammar ensures robust gene expression control through suboptimal transcription factor binding motifs, which reinforce the requirement for transcription factor cooperativity and create opportunities for fine-tuning enhancer activity levels.
“Another means by which flexible enhancer grammar ensures robust gene expression control is through “suboptimal” TF binding motifs, which reinforce the requirement for TF cooperativity and create opportunities for fine-tuning enhancer activity levels [125–128].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [125]
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Experimental — accuracy not yet measuredStrengthening transcription factor binding sites at developmental enhancers results in aberrant gene expression patterns.
“Consistent with this, “strengthening” TF binding sites at developmental enhancers results in aberrant gene expression patterns [125].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [125]
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- Authors
- Farley, E. K., Olson, K. M., Zhang, W., Brandt, A. J., Rokhsar, D. S., & Levine, M. S.
- Affiliations
- Princeton University (US)
- University of California San Diego (US)
- University of California, Berkeley (US)
- Corresponding author
- Farley, Emma K.
- Levine, Michael S.
- Venue
- Science
- Published
- 2015-10-16
- Volume
- 350
- Issue
- 6258
- Pages
- 325-328
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4970741
- OpenAlex
- W2308616703
- Cited by
- 319
- References
- 5
- Citations by year
- 2026: 18 · 2025: 25 · 2024: 47 · 2023: 30 · 2022: 32 · 2021: 28 · 2020: 39 · 2019: 26 · 2018: 25 · 2017: 26 · 2016: 22 · 2015: 1
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (GM46638, NS076542)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- enhancers, Ciona intestinalis, FGF signaling, GATA binding sites, ETS transcription factors, super-enhancers, developmental gene regulation
- MeSH terms
- Animals, Base Sequence, Binding Sites, Ciona intestinalis, Enhancer Elements, Genetic, Fibroblast Growth Factors, Molecular Sequence Data, Organ Specificity, Consensus Sequence, Gene Expression Regulation, Developmental, GATA Transcription Factors, Otx Transcription Factors, Fas-Associated Death Domain Protein
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