A core transcriptional network for early mesoderm development in Drosophila melanogaster
Open accessAbstract
Embryogenesis is controlled by large gene-regulatory networks, which generate spatially and temporally refined patterns of gene expression. Here, we report the characteristics of the regulatory network orchestrating early mesodermal development in the fruitfly Drosophila , where the transcription factor Twist is both necessary and sufficient to drive development. Through the integration of chromatin immunoprecipitation followed by microarray analysis (ChIP-on-chip) experiments during discrete time periods with computational approaches, we identified >2000 Twist-bound cis -regulatory modules (CRMs) and almost 500 direct target genes. Unexpectedly, Twist regulates an almost complete cassette of genes required for cell proliferation in addition to genes essential for morophogenesis and cell migration. Twist targets almost 25% of all annotated Drosophila transcription factors, which may represent the entire set of regulators necessary for the early development of this system. By combining in vivo binding data from Twist, Mef2, Tinman, and Dorsal we have constructed an initial transcriptional network of early mesoderm development. The network topology reveals extensive combinatorial binding, feed-forward regulation, and complex logical outputs as prevalent features. In addition to binary activation and repression, we suggest that Twist binds to almost all mesodermal CRMs to provide the competence to integrate inputs from more specialized transcription factors.
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Five novel Dorsal-binding and six novel Twist-binding cis-regulatory sequences were confirmed.
“Five novel Dorsal-binding (Zeitlinger et al. 2007) and six novel Twistbinding cis-regulatory sequences (Sandmann et al. 2007) were confirmed.”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Sandmann et al. 2007
Twist and Snail transcription factors play an instrumental role in controlling invagination and ventral furrow formation by regulated expression of the genes folded-gastrulation, concertina, and T48.
“Twist and Snail transcription factors play an instrumental role in controlling invagination and ventral furrow formation by regulated expression of the genes folded-gastrulation, concertina, and T48”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Sandmann et al. 2007
ChIP-chip methodology identified in vivo binding site occupancy for Dorsal, Twist, and Snail transcription factors.
“Experiments to identify cis-regulatory regions using ChIP-chip methodology were able to identify in vivo binding site occupancy for Dorsal, Twist, and Snail transcription factors”
From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Sandmann et al. 2007
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- Authors
- Sandmann, T., Girardot, C., Brehme, M., Tongprasit, W., Stolc, V., & Furlong, E. E. M.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Ames Research Center (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-02-15
- Volume
- 21
- Issue
- 4
- Pages
- 436-449
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1804332
- OpenAlex
- W2127043599
- Cited by
- 286
- References
- 76
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 8 · 2021: 18 · 2020: 7 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 15 · 2015: 19 · 2014: 17 · 2013: 13 · 2012: 21
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Genes & Development (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- Twist transcription factor, Drosophila melanogaster, cis-regulatory modules, transcriptional regulatory networks, direct target genes, MEF2, tinman, Dorsal, feedforward control, cell proliferation, cell migration, morphogenesis, network topology
- MeSH terms
- Animals, Drosophila melanogaster, Enhancer Elements, Genetic, Mesoderm, Gene Expression Regulation, Developmental, Drosophila Proteins, Embryonic Development, Chromatin Immunoprecipitation, Twist-Related Protein 1, Gene Regulatory Networks
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