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bioRxiv · 10.1101/820605

Regenerative capacity in Drosophila imaginal discs is controlled by damage-responsive, maturity-silenced enhancers

Harris, R. E.·Stinchfield, M. J.·Nystrom, S. L.·McKay, D. J.·Hariharan, I. K.
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Abstract

Like tissues of many organisms, Drosophila imaginal discs lose the ability to regenerate as they mature. This loss of regenerative capacity coincides with reduced damage-responsive expression of multiple genes needed for regeneration. Our previous work showed that two such genes, wg and Wnt6, are regulated by a single damage-responsive enhancer, which becomes progressively inactivated via Polycomb-mediated silencing as discs mature. Here we explore the generality of this mechanism, and identify numerous damage-responsive, maturity-silenced (DRMS) enhancers, some near genes known to be required for regeneration such as Mmp1, as well as near genes that we now show function in regeneration. Using a novel GAL4-independent tissue ablation system we characterize two DRMS-associated genes, apontic (apt), which curtails regeneration and CG9752/asperous (aspr), which promotes it. This mechanism of suppressing regeneration by silencing damage-responsive enhancers at multiple loci can be partially overcome by reducing activity of the chromatin regulator extra sex combs (esc).

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Harris, R. E., Stinchfield, M. J., Nystrom, S. L., McKay, D. J., Hariharan, I. K.. 2019-10-28. Regenerative capacity in Drosophila imaginal discs is controlled by damage-responsive, maturity-silenced enhancers. https://doi.org/10.1101/820605

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