Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo
Open accessAbstract
Segmentation of the Drosophila embryo begins with the establishment of spatially restricted gap gene-expression patterns in response to broad gradients of maternal transcription factors, such as Bicoid. Numerous studies have documented the fidelity of these expression patterns, even when embryos are subjected to genetic or environmental stress, but the underlying mechanisms for this transcriptional precision are uncertain. Here we present evidence that every gap gene contains multiple enhancers with overlapping activities to produce authentic patterns of gene expression. For example, a recently identified hunchback ( hb ) enhancer (located 5-kb upstream of the classic enhancer) ensures repression at the anterior pole. The combination of intronic and 5′ knirps ( kni ) enhancers produces a faithful expression pattern, even though the intronic enhancer alone directs an abnormally broad expression pattern. We present different models for “enhancer synergy,” whereby two enhancers with overlapping activities produce authentic patterns of gene expression.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In Drosophila, eve expression is controlled by five separate enhancers to produce stripe patterning in the embryo.
“In Drosophila, eve expression is controlled by five separate enhancers to produce stripe patterning in the embryo [483].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [483]
Cites
CANALIZATION OF DEVELOPMENT AND THE INHERITANCE OF ACQUIRED CHARACTERS
WADDINGTON, C. H. (1942) · Nature · doi:10.1038/150563a0 · Cited by 3,255 · cited 1× · see citing works
“It was proposed that shadow enhancers represent a mechanism of “canalization” (4), whereby populations of embryos develop normally even when subject to variations in temperature or genetic background.”
BackgroundShadow enhancers as a source of evolutionary novelty
Hong, J.-W., Hendrix, D. A., & Levine, M. S. (2008) · Science · doi:10.1126/science.1160631 · Cited by 474 · see citing works
Self-citationA regulatory code for neurogenic gene expression in the<i>Drosophila</i>embryo
Markstein, M., Zinzen, R., Markstein, P., Yee, K.-P., Erives, A., Stathopoulos, A., & Levine, M. (2004) · Development · doi:10.1242/dev.01124 · Cited by 165 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Transcription factors: from enhancer binding to developmental control
Spitz, F., & Furlong, E. E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3207 · Cited by 2,227 · see citing works
Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq
Arnold, C. D., Gerlach, D., Stelzer, C., Boryń, Ł. M., Rath, M., & Stark, A. (2013) · Science · doi:10.1126/science.1232542 · Cited by 1,125 · see citing works
Evidence for additive and synergistic action of mammalian enhancers during cell fate determination
Choi, J., Lysakovskaia, K., Stik, G., Demel, C., Söding, J., Tian, T. V., Graf, T., & Cramer, P. (2021) · eLife · doi:10.7554/elife.65381 · Cited by 117 · see citing works
“Indeed, expression of gap genes in Drosophila are regulated by multiple enhancers, and deleting one of these enhancers has little effect on the gene expression pattern (Perry et al., 2011).”
BackgroundTranscriptional 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
Khoueiry, P., Girardot, C., Ciglar, L., Peng, P.-C., Gustafson, E. H., Sinha, S., & Furlong, E. E. (2017) · eLife · doi:10.7554/elife.28440 · Cited by 44 · see citing works
Signal Integration by Shadow Enhancers and Enhancer Duplications Varies across the Drosophila Embryo
Scholes, C., Biette, K. M., Harden, T. T., & DePace, A. H. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.115 · Cited by 44 · see citing works
Spatial promoter–enhancer hubs in cancer: organization, regulation, and function
Zhao, J., & Faryabi, R. B. (2023) · Trends in Cancer · doi:10.1016/j.trecan.2023.07.017 · Cited by 28 · see citing works
Multiple conserved regulatory domains promote Fezf2 expression in the developing cerebral cortex
Eckler, M. J., Larkin, K. A., McKenna, W. L., Katzman, S., Guo, C., Roque, R., Visel, A., Rubenstein, J. L. L., & Chen, B. (2014) · Neural Development · doi:10.1186/1749-8104-9-6 · Cited by 27 · see citing works
Disparate expression specificities coded by a shared Hox-C enhancer
Miller, S. W., & Posakony, J. W. (2020) · eLife · doi:10.7554/elife.39876 · Cited by 4 · see citing works
- Authors
- Perry, M. W., Boettiger, A. N., & Levine, M.
- Affiliations
- Department of Integrative Biology,
- Biophysics Graduate Group,
- University of California, Berkeley (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-08-08
- Volume
- 108
- Issue
- 33
- Pages
- 13570-13575
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3158186
- OpenAlex
- W2077122170
- Cited by
- 228
- References
- 3
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 16 · 2023: 13 · 2022: 15 · 2021: 18 · 2020: 13 · 2019: 18 · 2018: 21 · 2017: 15 · 2016: 20 · 2015: 14 · 2014: 15 · 2013: 19 · 2012: 15
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- UC Berkeley College of Chemistry
- National Institute of General Medical Sciences (R01GM034431, GM34431)
- 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
- gap genes, enhancer redundancy, Drosophila embryo, hunchback, knirps, embryonic segmentation, intronic enhancer
- MeSH terms
- Animals, Drosophila melanogaster, Embryo, Nonmammalian, Embryonic Induction, Enhancer Elements, Genetic, Transcription Factors, Gene Expression Regulation, Developmental, Body Patterning, GTPase-Activating Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
