Design flexibility in cis-regulatory control of gene expression: Synthetic and comparative evidence
Open accessAbstract
In early Drosophila embryos, the transcription factor Dorsal regulates patterns of gene expression and cell fate specification along the dorsal-ventral axis. How gene expression is produced within the broad lateral domain of the presumptive neurogenic ectoderm is not understood. To investigate transcriptional control during neurogenic ectoderm specification, we examined divergence and function of an embryonic cis-regulatory element controlling the gene short gastrulation (sog). While transcription factor binding sites are not completely conserved, we demonstrate that these sequences are bona fide regulatory elements, despite variable regulatory architecture. Mutation of conserved sequences revealed that putative transcription factor binding sites for Dorsal and Zelda, a ubiquitous maternal transcription factor, are required for proper sog expression. When Zelda and Dorsal sites are paired in a synthetic regulatory element, broad lateral expression results. However, synthetic regulatory elements that contain Dorsal and an additional activator also drive expression throughout the neurogenic ectoderm. Our results suggest that interaction between Dorsal and Zelda drives expression within the presumptive neurogenic ectoderm, but they also demonstrate that regulatory architecture directing expression in this domain is flexible. We propose a model for neurogenic ectoderm specification in which gene regulation occurs at the intersection of temporal and spatial transcription factor inputs.
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In the syncytial Drosophila embryo, spatial stripes of dorsal/ventral and anterior/posterior regulatory gene expression are generated by parallel cis-regulatory responses to maternal and zygotic combinations of diffusing transcription factors.
“In the syncytial embryo spatial stripes of both dorsal/ventral and anterior/posterior regulatory gene expression, which specify the future multicellular embryonic territories, are generated by parallel cis-regulatory responses to maternally localized and zygotically expressed combinations of diffusing transcription factors15–17.”
From Emerging properties of animal gene regulatory networks (2010) · cites this paper as [16]
Recent evidence shows that positions where cis-regulatory modules act depend on combinatorial activator and repressor inputs, and morphogen concentrations alone do not predict target expression domains except sometimes at extreme high concentrations.
“Much recent evidence, however, shows that the positions where these cis-regulatory modules act depend on combinatorial activator and repressor inputs15–19, and the quantitative values of these ‘morphogens’ alone do not by themselves predict the spatial expression domains of their target genes (except sometimes at the extreme positions where their concentrations are highest).”
From Emerging properties of animal gene regulatory networks (2010) · cites this paper as [16]
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- Authors
- Liberman, L. M., & Stathopoulos, A.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Stathopoulos, Angelike
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 327
- Issue
- 2
- Pages
- 578-589
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC2746413
- OpenAlex
- W2076937905
- Cited by
- 76
- References
- 58
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 11 · 2014: 7 · 2013: 3 · 2012: 8
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1599 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Biology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, other-oa)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- University of Pennsylvania
- Searle Scholars Program
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM077668)
- 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
- cis-regulatory elements, Dorsal, Zelda, short gastrulation, dorsal-ventral axis, transcription factor binding sites, Drosophila embryo, gene expression regulation, transcriptional regulation
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, DNA Mutational Analysis, Drosophila, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Regulatory Sequences, Nucleic Acid, Transcription Factors, In Situ Hybridization, Genes, Reporter, Gene Expression Regulation, Developmental, Evolution, Molecular, Body Patterning, Drosophila Proteins, Animals, Genetically Modified
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