TY - JOUR TI - Damage-responsive, maturity-silenced enhancers regulate multiple genes that direct regeneration in Drosophila AU - Harris, Robin E AU - Stinchfield, Michael J AU - Nystrom, Spencer L AU - McKay, Daniel J AU - Hariharan, Iswar K A2 - Bellen, Hugo J A2 - Banerjee, Utpal VL - 9 PY - 2020 DA - 2020/06/03 SP - e58305 C1 - eLife 2020;9:e58305 DO - 10.7554/eLife.58305 UR - https://doi.org/10.7554/eLife.58305 AB - 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. We previously showed that two such genes, wg and Wnt6, are regulated by a single damage-responsive enhancer that becomes progressively inactivated via Polycomb-mediated silencing as discs mature (Harris et al., 2016). Here we explore the generality of this mechanism and identify additional damage-responsive, maturity-silenced (DRMS) enhancers, some near genes known to be required for regeneration such as Mmp1, and others near genes that we now show function in regeneration. Using a novel GAL4-independent 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). KW - regeneration KW - enhancers KW - epigenetic KW - silencing JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -