Conversion of a dorsal‐dependent silencer into an enhancer: evidence for dorsal corepressors.
Open accessAbstract
In Drosophila, the dorsal (dl) morphogen gradient initiates the differentiation of the embryonic mesoderm and neuroectoderm by activating the expression of regulatory genes (e.g. twist and snail) in a concentration-dependent manner. dl also functions as a repressor that establishes the dorsal epidermis and amnioserosa by restricting regulatory genes such as dpp and zen to dorsal regions of the embryo. The ability of dl to function as both an activator and repressor distinguishes it from the bicoid morphogen, which appears to function solely as an activator. In an effort to determine how dl functions as a repressor we have performed a detailed characterization of a zen silencer element, called the VRE, which mediates ventral repression in response to the dl gradient. A minimal 110 bp VRE sequence is identified, which is able to silence the ventral expression of a heterologous promoter. This sequence contains two dl binding sites as well as binding sites for additional nuclear factors present in early embryos. Mutations in the latter binding sites convert the minimal VRE into an enhancer, which mediates transcriptional activation in ventral regions in response to dl. These results suggest that dl is intrinsically an activator, but is converted into a potent silencer when it interacts with neighboring corepressors.
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Synergistic DNA binding between Dorsal and Twist, a bHLH transcription factor, permits gene expression in more lateral regions of the embryo where neither Dorsal nor Twist is capable of inducing gene expression independently.
“synergistic DNA binding between Dorsal and Twist, a bHLH transcription factor, permits gene expression in more lateral regions of the embryo where neither Dorsal nor Twist is capable of inducing gene expression independently”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Jiang and Levine 1993
The Discussion (page unavailable) says efficient Dorsal activation requires synergistic interactions with bHLH proteins. It does not identify Twist as the partner or describe synergistic DNA binding that permits expression in more lateral regions. The Introduction (page unavailable) instead says low levels of Dorsal activate genes such as rhomboid in lateral regions, so it does not support the assertion that Dorsal cannot induce expression there independently. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA twi cis-regulatory sequence that normally directs expression to ventral regions exhibited a dorsally expanded expression domain when the low affinity Dorsal binding sites were mutated to high-affinity ones.
“A twi cis-regulatory sequence, which normally directs expression to ventral regions of the embryo, exhibited a dorsally expanded expression domain (i.e., the ventrolateral domain) when the low affinity Dorsal binding sites were mutated to highaffinity ones.”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Jiang and Levine 1993
The Mechanism of repression section (page unavailable) says the twi promoter has low-affinity Dorsal sites and is activated in ventral regions. It does not report replacing those sites with high-affinity ones or a dorsally expanded twi expression domain. Instead, it describes the reverse substitution in the zen VRE. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe 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 Jiang and Levine 1993
The Introduction (page unavailable) says that Dorsal’s effect depends on neighboring binding sites, and the Modes of repression section says nearby coactivators can help Dorsal activate transcription. But this paper does not identify a particular spatial relationship between Dorsal and Twist protein binding sites; its discussion of the twist promoter concerns sites bound by Dorsal. That specific part of the claim is unsupported. (LLM, conf=0.82)
Experimental — accuracy not yet measuredType 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 Jiang and Levine 1993
The Modes of repression section says Snail can block Dorsal-dependent activation in neuroectodermal gene expression, and the Discussion says efficient Dorsal activation requires synergy with other proteins. The Mechanism of repression section discusses differences in Dorsal-site affinity between the zen and twist regulatory elements. Our copy does not classify Type I and Type II genes or establish the claimed differences between those classes. (LLM, conf=0.78)
Experimental — accuracy not yet measuredTwist 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 Jiang and Levine 1993
The Discussion (page unavailable) says Dorsal's efficient activation requires synergistic interactions with other proteins, including bHLH proteins. It does not identify Twist as the synergistic partner or say that the interaction regulates both Type I and Type II target genes; the Introduction instead describes Twist as a gene activated by Dorsal. (LLM, conf=0.73)
Experimental — accuracy not yet measured
The affinity of Dorsal binding sites within cis-regulatory sequences influences the domain of target-gene expression.
“the affinity of Dorsal binding sites within cis-regulatory sequences was found to influence the domain of target-gene expression”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Jiang and Levine 1993
Classical studies based on the analysis of cis-regulatory sequences showed that Dorsal can function as either an activator or a repressor to control gene expression along the dorsoventral axis.
“First, classical studies based on the analysis of cis-regulatory sequences showed that Dorsal can function as either an activator or a repressor to control gene expression along the DV axis”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Jiang et al. 1993
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Research works printed but not linked: 2
- Kraut,R. (1991) Ph.D. Dissertation, Columbia University.
- Weintraub,S.J., Prater,C.A. and Dean,D.C. (1992) Nature, 358, 259–261. Zhang,C.-C. and Bienz,M. (1992) Proc. Natl Acad. Sci. USA, 89, 7511-7515.
Cited by
Sorted by citations
Conversion of Dorsal from an activator to a repressor by the global corepressor Groucho
Dubnicoff, T., Valentine, S. A., Chen, G., Shi, T., Lengyel, J. A., Paroush, Z., & Courey, A. J. (1997) · Genes & Development · doi:10.1101/gad.11.22.2952 · Cited by 155 · see citing works
Graded dorsal and differential gene regulation in the Drosophila embryo.
Reeves, G. T., & Stathopoulos, A. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000836 · Cited by 119 · see citing works
Papatsenko, D., & Levine, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409414102 · Cited by 82 · see citing works
Self-citationAn anteroposterior Dorsal gradient in the<i>Drosophila</i> embryo
Huang, A. M., Rusch, J., & Levine, M. (1997) · Genes & Development · doi:10.1101/gad.11.15.1963 · Cited by 59 · see citing works
Self-citation
- Authors
- Jiang, J., Cai, H., Zhou, Q., & Levine, M.
- Affiliations
- University of California San Diego (US)
- Venue
- The EMBO Journal
- Published
- 1993-08-01
- Volume
- 12
- Issue
- 8
- Pages
- 3201-3209
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC413587
- OpenAlex
- W1585313030
- Cited by
- 136
- References
- 0
- Citations by year
- 2025: 2 · 2024: 6 · 2022: 2 · 2021: 6 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 6 · 2013: 1 · 2012: 3
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-46638)
- 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 › Epigenetics and DNA Methylation
- Keywords
- VRE, corepressors, transcriptional repression, Drosophila embryogenesis, mesoderm differentiation, amnioserosa, Twist, snails, DPP, Bicoid, morphogen gradients, transcriptional activation
- MeSH terms
- Animals, Base Sequence, Binding Sites, DNA, Drosophila, Enhancer Elements, Genetic, Larva, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Transcription Factors, Drosophila Proteins
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