Modulation of tissue repair by regeneration enhancer elements

Junsu Kang, Jianxin Hu, Ravi Karra, Amy L. Dickson, Valerie A. Tornini, Gregory Nachtrab, Matthew Gemberling, Joseph A. Goldman, Brian L. Black and Kenneth D. Poss ()
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Junsu Kang: Duke University Medical Center
Jianxin Hu: Cardiovascular Research Institute, University of California
Ravi Karra: Duke University Medical Center
Amy L. Dickson: Duke University Medical Center
Valerie A. Tornini: Duke University Medical Center
Gregory Nachtrab: Duke University Medical Center
Matthew Gemberling: Duke University Medical Center
Joseph A. Goldman: Duke University Medical Center
Brian L. Black: Cardiovascular Research Institute, University of California
Kenneth D. Poss: Duke University Medical Center

Nature, 2016, vol. 532, issue 7598, 201-206

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/nature17644

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