Regeneration involves gene expression changes explained in part by context-dependent recruitment of transcriptional activators to distal enhancers. Silencers that engage repressive transcriptional complexes are less studied than enhancers and more technically challenging to validate, but they potentially have profound biological importance for regeneration. Here, we identified candidate silencers through a screening process that examined the ability of DNA sequences to limit injury-induced gene expression in larval zebrafish after fin amputation. A short sequence () on chromosome 5 near several genes that reduce expression during adult fin regeneration could suppress promoter activity in stable transgenic lines and diminish nearby gene expression in knockin lines. High-resolution analysis of chromatin organization identified physical associations of with gene promoters occurring preferentially during fin regeneration, and genomic deletion of elevated the expression of these genes after fin amputation. Our study provides methods to identify “tissue regeneration silencer elements” (TRSEs) with the potential to reduce unnecessary or deleterious gene expression during regeneration.

中文翻译：

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斑马鱼再生相关消音器调控元件的筛选

再生涉及基因表达变化，部分原因是转录激活因子向远端增强子的环境依赖性募集。与增强子相比，参与抑制性转录复合物的沉默子的研究较少，并且在技术上验证起来更具挑战性，但它们对再生可能具有深远的生物学重要性。在这里，我们通过筛选过程确定了候选沉默子，该筛选过程检查了DNA序列限制鳍截肢后斑马鱼幼体损伤诱导的基因表达的能力。5 号染色体上靠近几个在成体鳍再生过程中降低表达的基因附近的短序列 () 可以抑制稳定转基因系中的启动子活性，并减少敲入系中附近的基因表达。染色质组织的高分辨率分析确定了在鳍再生过程中优先发生的与基因启动子的物理关联，并且基因组删除在鳍截肢后提高了这些基因的表达。我们的研究提供了识别“组织再生沉默元件”（TRSE）的方法，有可能减少再生过程中不必要或有害的基因表达。