Phenotypic robustness conferred by apparently redundant transcriptional enhancers
Open accessAbstract
Genes include cis-regulatory regions that contain transcriptional enhancers. Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns: primary enhancers located near the basal promoter and secondary, or 'shadow', enhancers located at more remote positions. It has been proposed that the seemingly redundant activity of primary and secondary enhancers contributes to phenotypic robustness. We tested this hypothesis by generating a deficiency that removes two newly discovered enhancers of shavenbaby (svb, a transcript of the ovo locus), a gene encoding a transcription factor that directs development of Drosophila larval trichomes. At optimal temperatures for embryonic development, this deficiency causes minor defects in trichome patterning. In embryos that develop at both low and high extreme temperatures, however, absence of these secondary enhancers leads to extensive loss of trichomes. These temperature-dependent defects can be rescued by a transgene carrying a secondary enhancer driving transcription of the svb cDNA. Finally, removal of one copy of wingless, a gene required for normal trichome patterning, causes a similar loss of trichomes only in flies lacking the secondary enhancers. These results support the hypothesis that secondary enhancers contribute to phenotypic robustness in the face of environmental and genetic variability.
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Multiple enhancers may provide robustness in gene expression.
“From the data presented here and from others29, 30, it seems likely that multiple enhancers may provide robustness in gene expression.”
From Genetic dissection of the α-globin super-enhancer in vivo (2016) · cites this paper as [29]
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- Authors
- Frankel, N., Davis, G. K., Vargas, D., Wang, S., Payre, F., & Stern, D. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Bryn Mawr College (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Stern, David L.
- Venue
- Nature
- Published
- 2010-05-30
- Volume
- 466
- Issue
- 7305
- Pages
- 490-493
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2909378
- OpenAlex
- W1972013835
- Cited by
- 510
- References
- 2
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 41 · 2023: 29 · 2022: 24 · 2021: 29 · 2020: 50 · 2019: 38 · 2018: 31 · 2017: 22 · 2016: 20 · 2015: 28 · 2014: 31 · 2013: 38 · 2012: 36
- FWCI
- 17.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (R01GM063622, GM063622-06A1)
- 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, phenotypic robustness, trichome patterning, wingless, temperature sensitivity, cis-regulatory elements, embryonic development, Drosophila, enhancer redundancy, developmental gene regulation
- MeSH terms
- Animals, Animal Structures, DNA-Binding Proteins, Drosophila melanogaster, Enhancer Elements, Genetic, Larva, Models, Genetic, Phenotype, Temperature, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Developmental, Transgenes, Drosophila Proteins
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