Multi-enhancer transcriptional hubs confer phenotypic robustness.

We previously showed in embryos that low-affinity Ultrabithorax (Ubx)-responsive () enhancers drive expression using localized transcriptional environments and that active 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 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 -regulatory region inserted into a different chromosome colocalized with the locus, increasing Ubx concentration, the transcriptional output of , 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.