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Modulation of tissue repair by regeneration enhancer elements

机译：通过再生增强元件调节组织修复

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摘要

How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly 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.
机译：损伤触发组织再生程序的方式受到了有限的研究关注。在这里，我们研究了在再生组织中被激活的增强子调控元件的存在。转录组学分析显示，瘦素b（lepb）在斑马鱼的心脏和鳍再生中被高度诱导。表观遗传学分析鉴定了lepb上游和远端的短DNA序列元件，该元件在再生过程中获得了开放的染色质标记，并能够通过最少的启动子实现损伤依赖性表达。该元素可以激活受伤的新生小鼠组织中的表达，并且可以被组织特异性模块分割成足以在再生斑马鱼鳍或心脏中表达的元素。简单的增强子效应转基因采用前或反再生因子上游的lepb连锁序列控制斑马鱼再生的功效。我们的发现为“组织再生增强因子”（TREE）触发了损伤部位的基因表达提供了证据，并且可以被工程化以调节脊椎动物器官的再生潜力。

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  • 来源
    《Nature》 |2016年第7598期|201-206|共6页
  • 作者

    Kang Junsu; Hu Jianxin; Karra Ravi; Dickson Amy L.; Tornini Valerie A.; Nachtrab Gregory; Gemberling Matthew; Goldman Joseph A.; Black Brian L.; Poss Kenneth D.;

  • 作者单位

    Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA;

    Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA;

    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA;

    Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA;

    Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA;

    Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA;

    Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA;

    Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA;

    Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA;

    Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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