Arizona State University, Tempe, United States.
University of North Carolina at Chapel Hill, Chapel Hill, United States.
Elife. 2020 Jun 3;9:e58305. doi: 10.7554/eLife.58305.
Like tissues of many organisms, 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, and , 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 , and others near genes that we now show function in regeneration. Using a novel GAL4-independent ablation system we characterize two DRMS-associated genes, (), which curtails regeneration and CG9752/, 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 ().
与许多生物体的组织一样， 成虫盘随着成熟而失去再生能力。这种再生能力的丧失与再生所需的多个基因的损伤反应表达减少相吻合。我们之前曾表明，两个这样的基因， 和 ，受到一个单一的损伤反应增强子的调节，该增强子随着盘的成熟通过 Polycomb 介导的沉默而逐渐失活 (Harris 等人，2016)。在这里，我们探索了这种机制的普遍性，并确定了其他的损伤反应性、成熟沉默性（DRMS）增强子，一些在已知与再生相关的基因附近，如 ，而其他在我们现在显示在再生中起作用的基因附近。我们使用一种新的 GAL4 非依赖性消融系统来描述两个 DRMS 相关基因， （），它限制了再生，而 CG9752/，它促进了再生。通过在多个基因座上沉默损伤反应性增强子来抑制再生的这种机制可以通过降低染色质调节剂的活性来部分克服 （）。
