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Disruption of promoter-enhancer communication leads to engrailed mutants

poster
posted on 20.04.2020 by Anna G. Horacek, Victoria C. Blake, Judith A. Kassis
In Drosophila, the invected (inv) and engrailed (en) genes exist within a co-regulated complex and are expressed throughout early development. Although the inv/en promoters are separated by 54 kb, their expression is regulated by the same enhancers distributed across a 70 kb region, suggesting that enhancers can activate multiple promoters over long distances. Previous studies have identified a 2 kb regulatory fragment upstream of the en promotor, which may serve as a promoter tethering element by facilitating interactions between the en promoter and distant enhancers. We have generated a transgenic line containing the 2 kb regulatory fragment fused to a β-galactosidase reporter gene inserted near the en promoter. When coupled with a wild-type chromosome, transgenic organisms expressed β-galactosidase and En only in the posterior compartment of the wing imaginal discs, consistent with appropriate enhancer communication. However, in the absence of a wild-type chromosome, transgenic organisms exhibited impaired imaginal disc development in addition to a de-repression of β-galactosidase in the anterior compartment of the wing imaginal discs, suggesting the endogenous enhancers have been hijacked by the regulatory fragment within the transgene. Taken together, our data suggest that a specific regulatory fragment may serve as a promoter tethering element and is required to facilitate interactions between the en promoter and imaginal disc enhancers at discrete developmental stages.

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NICHD

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Program Number

863B

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