Modulation of tissue repair by regeneration enhancer elements.
Modulation of tissue repair by regeneration enhancer elements.
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DOI：
10.1038/nature17644
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发表时间：
2016-04-14
期刊：
影响因子：
64.8
通讯作者：
Poss KD
中科院分区：
文献类型：
--
作者：
Kang J;Hu J;Karra R;Dickson AL;Tornini VA;Nachtrab G;Gemberling M;Goldman JA;Black BL;Poss KD
组织再生程序是如何由损伤引发的，受到了有限的研究关注。在这里，我们调查了参与再生组织的增强子调控元件的存在。转录组分析表明，瘦素B（lep B）在斑马鱼的心脏和鳍再生中受到强烈诱导。表观遗传分析确定了一个短的DNA序列元件上游和远端lepb获得开放的染色质标记在再生过程中，并使损伤依赖性表达从最小的启动子。该元件可以激活在损伤的新生小鼠组织中的表达，并且可以分成足以在再生的斑马鱼鳍或心脏中表达的组织特异性模块。简单的增强子-效应子转基因采用lebb连锁序列上游的促或抗再生因子控制斑马鱼的再生功效。我们的研究结果为组织再生增强子元件（TREE）提供了证据，这些元件可以触发损伤部位的基因表达，并可以通过工程改造来调节脊椎动物器官的再生潜力。
How tissue regeneration programs are triggered by injury has received limited research attention. Here, we investigated the existence of enhancer regulatory elements that engage in regenerating tissue. Transcriptome analyses revealed that leptin b (lepb) is sharply induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for tissue regeneration enhancer elements (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.