Multi-enhancer transcriptional hubs confer phenotypic robustness
Abstract
We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and that active svb enhancers on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis that these multi-enhancer 'hubs' improve phenotypic resilience to stress by buffering against decreases in transcription factor concentrations and transcriptional output. Deleting a redundant enhancer from the svb locus led to reduced trichome numbers in embryos raised at elevated temperatures. Using high-resolution fluorescence microscopy, we observed lower Ubx concentration and transcriptional output in this deletion allele. Transcription sites of the full svb cis-regulatory region inserted into a different chromosome colocalized with the svb locus, increasing Ubx concentration, the transcriptional output of svb, and partially rescuing the phenotype. Thus, multiple enhancers could reinforce a local transcriptional hub to buffer against environmental stresses and genetic perturbations, providing a mechanism for phenotypical robustness.
Data availability
The original images (cuticle preparations and embryo images, organized into zip files) are available for download and are indexed at: https://www.embl.de/download/crocker/svb_enhancer_colocalization/index.html. Please note that the raw AiryScan images must be processed though the Zen software from Zeiss before they can be opened/analyzed using standard image processing softwares. These files are large, totaling up to approximately 180 GB in size. We can also send these files directly if a means of transfer (hard drives, etc.) is provided.
Article and author information
Author details
Funding
Damon Runyon Cancer Research Foundation (DRG 2220-15)
- Albert Tsai
European Molecular Biology Organization
- Albert Tsai
- Mariana R P Alves
- Justin Crocker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Tsai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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