Quantitative analysis of binding motifs mediating diverse spatial readouts of the Dorsal gradient in the Drosophila embryo
Open accessAbstract
Dorsal is a sequence-specific transcription factor that is distributed in a broad nuclear gradient across the dorsal–ventral (DV) axis of the early Drosophila embryo. It initiates gastrulation by regulating at least 30–50 target genes in a concentration-dependent fashion. Previous studies identified 18 enhancers that are directly regulated by different concentrations of Dorsal. Here, we employ computational methods to determine the basis for these distinct transcriptional outputs. Orthologous enhancers were identified in a variety of divergent Drosophila species, and their comparison revealed several conserved sequence features responsible for DV patterning. In particular, the quality of Dorsal and Twist recognition sequences correlates with the DV coordinates of gene expression relative to the Dorsal gradient. These findings are entirely consistent with a gradient threshold model for DV patterning, whereby the quality of individual Dorsal binding sites determines in vivo occupancy of target enhancers by the Dorsal gradient. Linked Dorsal and Twist binding sites constitute a conserved composite element in certain “type 2” Dorsal target enhancers, which direct gene expression in ventral regions of the neurogenic ectoderm in response to intermediate levels of the Dorsal gradient. Similar motif arrangements were identified in orthologous loci in the distant mosquito genome, Anopheles gambiae . We discuss how Dorsal and Twist work either additively or synergistically to activate different target enhancers.
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The organization of sites relative to each other, in particular the relationship between Dorsal and Twist transcription factors, may be important to support expression in given domains.
“Further analysis of cis-regulatory region architecture suggested that the organization of sites relative to each other, in particular of the relationship between Dorsal and Twist transcription factors, may be important to support expression in given domains”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Papatsenko and Levine 2005
Twist and Dorsal function in a synergistic manner to regulate expression of both Type I and Type II target genes.
“First, Twist and Dorsal function in a synergistic manner to regulate expression of both Type I and Type II target genes.”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Papatsenko and Levine 2005
Type II genes are distinguished from Type I genes because, generally, they are repressed by Sna and require higher-affinity Dorsal sites or stronger Dorsal/Twist synergy.
“Type II genes are distinguished from Type I genes because, generally, they are repressed by Sna and require higheraffinity Dorsal sites or stronger Dorsal/Twist synergy”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Papatsenko and Levine 2005
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Dynamic patterning by morphogens illuminated by cis-regulatory studies
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Role of sequence encoded κB DNA geometry in gene regulation by Dorsal
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An alignment-free method to identify candidate orthologous enhancers in multiple Drosophila genomes
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Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression
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Microfluidics for High-Throughput Quantitative Studies of Early Development
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- Authors
- Papatsenko, D., & Levine, M.
- Affiliations
- University of California, Berkeley (US)
- ORCID
- Levine, Michael
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-03-28
- Volume
- 102
- Issue
- 14
- Pages
- 4966-4971
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC555988
- OpenAlex
- W2087202849
- Cited by
- 82
- References
- 52
- Citations by year
- 2025: 3 · 2024: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 6
- FWCI
- 4.16
- 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
- National Institute of General Medical Sciences (R37GM046638, GM-46638, R01GM046638)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- 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
- Keywords
- dorsoventral patterning, Drosophila embryo, Twist, Anopheles gambiae, transcriptional synergy, gastrulation
- MeSH terms
- Animals, Base Sequence, Binding Sites, DNA, Drosophila melanogaster, Enhancer Elements, Genetic, Models, Genetic, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Phylogeny, Sequence Homology, Nucleic Acid, Transcription Factors, Conserved Sequence, Genes, Insect, Gene Expression Regulation, Developmental, Body Patterning, Drosophila Proteins, Twist-Related Protein 1
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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.
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