Hunchback (Hb) is a bifunctional transcription factor that activates and represses distinct enhancers. Here, we investigate the hypothesis that Hb can activate and repress the same enhancer. Computational models predicted that Hb bifunctionally regulates the even-skipped (eve) stripe 3+7 enhancer (eve3+7) in Drosophila blastoderm embryos. We measured and modeled eve expression at cellular resolution under multiple genetic perturbations and found that the eve3+7 enhancer could not explain endogenous eve stripe 7 behavior. Instead, we found that eve stripe 7 is controlled by two enhancers: the canonical eve3+7 and a sequence encompassing the minimal eve stripe 2 enhancer (eve2+7). Hb bifunctionally regulates eve stripe 7, but it executes these two activities on different pieces of regulatory DNA--it activates the eve2+7 enhancer and represses the eve3+7 enhancer. These two "shadow enhancers" use different regulatory logic to create the same pattern.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311800 | PMC |
| http://dx.doi.org/10.1073/pnas.1413877112 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modelling and calibration of pair-rule protein patterns in Drosophila embryo: From Even-skipped and Fushi-tarazu to Wingless expression networks.
Dev Biol
January 2025
University of Lisbon, IST, Dep. of Physics, Nonlinear Dynamics Group, Av. Rovisco Pais, 1049-001, Lisbon, Portugal. Electronic address:
We modelled and calibrated the distributions of the seven-stripe patterns of Even-skipped (Eve) and Fushi-tarazu (Ftz) pair-rule proteins along the anteroposterior axis of the Drosphila embryo, established during early development. We have identified the putative repressive combinations for five Eve enhancers, and we have explored the relationship between Eve and Ftz for complementary patterns. The regulators of Eve and Ftz are stripe-specific DNA enhancers with embryo position-dependent activation rates and are regulated by the gap family of proteins.
View Article and Find Full Text PDFStem-loop and circle-loop TADs generated by directional pairing of boundary elements have distinct physical and regulatory properties.
Elife
August 2024
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, United States.
The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs are formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing interactions between boundaries are typically orientation-dependent.
View Article and Find Full Text PDFMultifaceted effects on even-skipped transcriptional dynamics upon Krüppel dosage changes.
Development
March 2024
Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Although fluctuations in transcription factor (TF) dosage are often well tolerated, TF dosage modulation can change the target gene expression dynamics and result in significant non-lethal developmental phenotypes. Using MS2/MCP-mediated quantitative live imaging in early Drosophila embryos, we analyzed how changing levels of the gap gene Krüppel (Kr) affects transcriptional dynamics of the pair-rule gene even-skipped (eve). Halving the Kr dosage leads to a transient posterior expansion of the eve stripe 2 and an anterior shift of stripe 5.
View Article and Find Full Text PDFMulti-level regulation of even-skipped stripes by the ubiquitous factor Zelda.
Development
December 2023
Department of Biology, Hamilton College, 198 College Hill Rd., Clinton, NY 13323, USA.
The zinc-finger protein Zelda (Zld) is a key activator of zygotic transcription in early Drosophila embryos. Here, we study Zld-dependent regulation of the seven-striped pattern of the pair-rule gene even-skipped (eve). Individual stripes are regulated by discrete enhancers that respond to broadly distributed activators; stripe boundaries are formed by localized repressors encoded by the gap genes.
View Article and Find Full Text PDFFunctional analysis of the Drosophila eve locus in response to non-canonical combinations of gap gene expression levels.
Dev Cell
December 2023
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544, USA; Department of Stem Cell and Developmental Biology, CNRS UMR3738 Paris Cité, Institut Pasteur, 75015 Paris, France. Electronic address:
Transcription factor combinations play a key role in shaping cellular identity. However, the precise relationship between specific combinations and downstream effects remains elusive. Here, we investigate this relationship within the context of the Drosophila eve locus, which is controlled by gap genes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!