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Multi-enhancer transcriptional hubs confer phenotypic robustness.
Albert Tsai1, Mariana Rp Alves1,2, Justin Crocker1
1European Molecular Biology Laboratory, Heidelberg, Germany.
Elife
|July 12, 2019
Summary
Multiple enhancers form transcriptional hubs that enhance resilience to environmental stress by maintaining gene expression. This study demonstrates how these hubs buffer against fluctuations in transcription factor levels, ensuring robust development in Drosophila embryos.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Previous work showed low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers utilize localized transcriptional environments.
- Active svb enhancers on different chromosomes tend to colocalize, forming potential multi-enhancer hubs.
Purpose of the Study:
- To test the hypothesis that multi-enhancer hubs improve phenotypic resilience to stress.
- To investigate if these hubs buffer against decreases in transcription factor concentrations and transcriptional output.
Main Methods:
- Deletion of a redundant enhancer from the svb locus.
- High-resolution fluorescence microscopy to observe Ubx concentration and transcriptional output.
- Insertion of the full svb cis-regulatory region into a different chromosome.
Main Results:
- Deleting a redundant enhancer reduced trichome numbers in embryos at elevated temperatures.
- The deletion allele showed lower Ubx concentration and transcriptional output.
- Colocalization of transcription sites with the svb locus increased Ubx concentration and transcriptional output, partially rescuing the phenotype.
Conclusions:
- Multiple enhancers can reinforce a local transcriptional hub.
- These hubs buffer against environmental stresses and genetic perturbations.
- This provides a mechanism for phenotypical robustness.
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