ArticleProceedings of the National Academy of Sciences of the United States of America2003
Transcriptional regulatory cascades in development: initial rates, not steady state, determine network kinetics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed.
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- Programmed Double-stranded RNA Formation Enables Meiotic Stage Transitions.bioRxiv : the preprint server for biology · 2026Article
- Transcriptional regulation of neuropeptide receptors underlies context-dependent adaptation in Drosophila melanogaster.FEBS open bio · 2026Article
- Isoform-Specific Transcriptomic Effects ofGenes · 2025Article
- Combinatorial regulatory states define cell fate diversity during embryogenesis.Nature communications · 2024Article
- Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns.BMC genomics · 2024Article
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- Engineering activatable promoters for scalable and multi-input CRISPRa/i circuits.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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- Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient.Cell systems · 2023Article
- Context-Aware Technology Mapping in Genetic Design Automation.ACS synthetic biology · 2023Article
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- mCell proliferation · 2022Article
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- Chemical chaperones reverse early suppression of regulatory circuits during unfolded protein response in B cells from common variable immunodeficiency patients.Clinical and experimental immunology · 2020Article
- Constructing temporal regulatory cascades in the context of development and cell differentiation.PloS one · 2020Article
- Causal Gene Regulatory Network Modeling and Genomics: Second-Generation Challenges.Journal of computational biology : a journal of computational molecular cell biology · 2019Article
- How Does the Regulatory Genome Work?Journal of computational biology : a journal of computational molecular cell biology · 2019Article
- Encounters across networks: Windows into principles of genomic regulation.Marine genomics · 2019Article
- Spatial and temporal patterns of gene expression during neurogenesis in the sea urchinEvoDevo · 2019Article
45 more citing papers are in PubMed but not listed here.
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2 authors.
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Abstract
A model was built to examine the kinetics of regulatory cascades such as occur in developmental gene networks. The model relates occupancy of cis-regulatory target sites to transcriptional initiation rate, and thence to RNA and protein output. The model was used to simulate regulatory cascades in which genes encoding transcription factors are successively activated. Using realistic parameter ranges based on extensive earlier measurements in sea urchin embryos, we find that transitions of regulatory states occur sharply in these simulations, with respect to time or changing transcription factor concentrations. As is often observed in developing systems, the simulated regulatory cascades display a succession of gene activations separated by delays of some hours. The most important causes of this behavior are cooperativity in the assembly of cis-regulatory complexes and the high specificity of transcription factors for their target sites. Successive transitions in state occur long in advance of the approach to steady-state levels of the molecules that drive the process. The kinetics of such developmental systems thus depend mainly on the initial output rates of genes activated in response to the advent of new transcription factors.
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