ArticleMechanisms of development2014
Deciphering the combinatorial architecture of a Drosophila homeotic gene enhancer.
Article in Mechanisms of development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 20 citations in OpenAlex.
- Study of the Role of Transvection in the Regulation of Initiators That Determine Activity of the Regulatory Domains of the Drosophila melanogaster Abd-B Gene.Doklady. Biochemistry and biophysics · 2026Article
- Initiators counteract Polycomb repression and stimulate long-range contacts between enhancers and theOpen biology · 2025Article
- Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA.Biochimica et biophysica acta. Gene regulatory mechanisms · 2025Review
- Two coacting shadow enhancers regulate twin of eyeless expression during early Drosophila development.Genetics · 2025Article
- Boundary bypass activity in theOpen biology · 2023Article
- Transcriptional Readthrough Interrupts Boundary Function in Drosophila.International journal of molecular sciences · 2023Article
- Boundary Bypass Activity in thebioRxiv : the preprint server for biology · 2023Article
- Transcriptional read through interrupts boundary function in Drosophila.bioRxiv : the preprint server for biology · 2023Article
- Mechanisms of Interaction between Enhancers and Promoters in ThreeInternational journal of molecular sciences · 2023Review
- Fitting thermodynamic-based models: Incorporating parameter sensitivity improves the performance of an evolutionary algorithm.Mathematical biosciences · 2021Article
- Redundant enhancers in the iab-5 domain cooperatively activate Abd-B in the A5 and A6 abdominal segments of Drosophila.Development (Cambridge, England) · 2021Article
- Mapping of functional elements of the Fab-6 boundary involved in the regulation of the Abd-B hox gene in Drosophila melanogaster.Scientific reports · 2021Article
- Homeotic Genes: Clustering, Modularity, and Diversity.Frontiers in cell and developmental biology · 2021Review
- Rapid and efficient purification of Drosophila homeodomain transcription factors for biophysical characterization.Protein expression and purification · 2019Article
- Spatial distribution of predicted transcription factor binding sites in Drosophila ChIP peaks.Mechanisms of development · 2016Article
- Article
- Nucleotide Interdependency in Transcription Factor Binding Sites in the Drosophila Genome.Gene regulation and systems biology · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
In Drosophila, the 330 kb bithorax complex regulates cellular differentiation along the anterior–posterior axis during development in the thorax and abdomen and is comprised of three homeotic genes: Ultrabithorax, abdominal-A, and Abdominal-B. The expression of each of these genes is in turn controlled through interactions between transcription factors and a number of cis-regulatory modules in the neighboring intergenic regions. In this study, we examine how the sequence architecture of transcription factor binding sites mediates the functional activity of one of these cis-regulatory modules. Using computational, mathematical modeling and experimental molecular genetic approaches we investigate the IAB7b enhancer, which regulates Abdominal-B expression specifically in the presumptive seventh and ninth abdominal segments of the early embryo. A cross-species comparison of the IAB7b enhancer reveals an evolutionarily conserved signature motif containing two FUSHI-TARAZU activator transcription factor binding sites. We find that the transcriptional repressors KNIRPS, KRUPPEL and GIANT are able to restrict reporter gene expression to the posterior abdominal segments, using different molecular mechanisms including short-range repression and competitive binding. Additionally, we show the functional importance of the spacing between the two FUSHI-TARAZU binding sites and discuss the potential importance of cooperativity for transcriptional activation. Our results demonstrate that the transcriptional output of the IAB7b cis-regulatory module relies on a complex set of combinatorial inputs mediated by specific transcription factor binding and that the sequence architecture at this enhancer is critical to maintain robust regulatory function.
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