Modulation of tissue repair by regeneration enhancer elements.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kang, J; Hu, J; Karra, R; Dickson, AL; Tornini, VA; Nachtrab, G; Gemberling, M; Goldman, JA; Black, BL; Poss, KD

Published Date

  • April 6, 2016

Published In

Volume / Issue

  • 532 / 7598

Start / End Page

  • 201 - 206

PubMed ID

  • 27049946

Pubmed Central ID

  • 27049946

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature17644

Language

  • eng