Damage-responsive, maturity-silenced enhancers regulate multiple genes that direct regeneration in <i>Drosophila</i>.

Abstract

Like tissues of many organisms, <i>Drosophila</i> 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, <i>wg</i> and <i>Wnt6</i>, 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 <i>Mmp1</i>, and others near genes that we now show function in regeneration. Using a novel GAL4-independent ablation system we characterize two DRMS-associated genes, <i>apontic</i> (<i>apt</i>), which curtails regeneration and CG9752/<i>asperous (aspr)</i>, 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 <i>extra sex combs</i> (<i>esc</i>).