Modulation of tissue repair by regeneration enhancer elements

被引:0
|
作者
Junsu Kang
Jianxin Hu
Ravi Karra
Amy L. Dickson
Valerie A. Tornini
Gregory Nachtrab
Matthew Gemberling
Joseph A. Goldman
Brian L. Black
Kenneth D. Poss
机构
[1] Duke University Medical Center,Department of Cell Biology
[2] Cardiovascular Research Institute,Department of Medicine
[3] University of California,undefined
[4] Duke University Medical Center,undefined
来源
Nature | 2016年 / 532卷
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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.
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页码:201 / 206
页数:5
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