ArticleDevelopment (Cambridge, England)2008
Multiple modular promoter elements drive graded brinker expression in response to the Dpp morphogen gradient.
Article in Development (Cambridge, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- A genome-engineered tool set for Drosophila TGF-β/BMP signaling studies.Development (Cambridge, England) · 2024Article
- Enhancer redundancy in development and disease.Nature reviews. Genetics · 2021Review
- BMP-dependent gene repression cascade in Drosophila eggshell patterning.Developmental biology · 2015Article
- CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster.Cell cycle (Georgetown, Tex.) · 2015Article
- Co-regulation of invected and engrailed by a complex array of regulatory sequences in Drosophila.Developmental biology · 2014Article
- Temporal regulation of Dpp signaling output in the Drosophila wing.Developmental dynamics : an official publication of the American Association of Anatomists · 2014Article
- In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression.Journal of bioinformatics and computational biology · 2014Article
- Quantitative modeling of a gene's expression from its intergenic sequence.PLoS computational biology · 2014Article
- Simulations of enhancer evolution provide mechanistic insights into gene regulation.Molecular biology and evolution · 2014Article
- MEF2 is an in vivo immune-metabolic switch.Cell · 2013Article
- Autoregulatory feedback controls sequential action of cis-regulatory modules at the brinker locus.Developmental cell · 2013Article
- Brk regulates wing disc growth in part via repression of Myc expression.EMBO reports · 2013Article
- Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements.Development (Cambridge, England) · 2013Article
- Manipulating the sensitivity of signal-induced repression: quantification and consequences of altered brinker gradients.PloS one · 2013Article
- Transcription factors: from enhancer binding to developmental control.Nature reviews. Genetics · 2012Review
- Response to the BMP gradient requires highly combinatorial inputs from multiple patterning systems in the Drosophila embryo.Development (Cambridge, England) · 2012Article
- Ancestral and conserved cis-regulatory architectures in developmental control genes.Developmental biology · 2012Article
- Shadow enhancers: frequently asked questions about distributed cis-regulatory information and enhancer redundancy.BioEssays : news and reviews in molecular, cellular and developmental biology · 2012Article
- Groucho-mediated repression may result from a histone deacetylase-dependent increase in nucleosome density.PloS one · 2010Article
- Spatial discontinuity of optomotor-blind expression in the Drosophila wing imaginal disc disrupts epithelial architecture and promotes cell sorting.BMC developmental biology · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Morphogen gradients play fundamental roles in patterning and cell specification during development by eliciting differential transcriptional responses in target cells. In Drosophila, Decapentaplegic (Dpp), the BMP2/4 homolog, downregulates transcription of the nuclear repressor brinker (brk) in a concentration-dependent manner to generate an inverse graded distribution. Both Dpp and Brk are crucial for directing Dpp target gene expression in defined domains and the consequent execution of distinct developmental programs. Thus, determining the mechanism by which the brk promoter interprets the Dpp activity gradient is essential for understanding both Dpp-dependent patterning and how graded signaling activity can generate different responses through transcriptional repression. We have uncovered key features of the brk promoter that suggest it uses a complex enhancer logic not represented in current models. First, we find that the regulatory region contains multiple compact modules that can independently drive brk-like expression patterns. Second, each module contains binding sites for the Schnurri/Mad/Medea (SMM) complex, which mediates Dpp-dependent repression, linked to regions that direct activation. Third, the SMM repression complex acts through a distance-dependent mechanism that probably uses the canonical co-repressor C-terminal Binding Protein (CtBP). Finally, our data suggest that inputs from multiple regulatory modules are integrated to generate the final pattern. This unusual promoter organization may be necessary for brk to respond to the Dpp gradient in a precise and robust fashion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.