Damage-responsive, maturity-silenced enhancers regulate multiple genes that direct regeneration in Drosophila

• DOI: 10.7554/elife.58305
• Publication Date: 2020-06-03T12:01:05Z
• Authors: Robin E Harris; Michael J Stinchf...; Spencer L Nystrom; Daniel J McKay; Iswar K Hariharan
• Keywords: 0301 basic medicine; QH301-705.5; Science; Q; R; Gene Expression Regulation, Developmental; 03 medical and health sciences; Drosophila melanogaster; Enhancer Elements, Genetic; Imaginal Discs; regeneration; silencing; Medicine; Animals; Drosophila Proteins; Regeneration; enhancers; Gene Silencing; Biology (General); epigenetic; Developmental Biology

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).