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Modulation of tissue repair by regeneration enhancer elements.

Publication ,  Journal Article
Kang, J; Hu, J; Karra, R; Dickson, AL; Tornini, VA; Nachtrab, G; Gemberling, M; Goldman, JA; Black, BL; Poss, KD
Published in: Nature
April 14, 2016

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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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

April 14, 2016

Volume

532

Issue

7598

Start / End Page

201 / 206

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Wound Healing
  • Transgenes
  • Regeneration
  • Promoter Regions, Genetic
  • Organ Specificity
  • Myocytes, Cardiac
  • Mice
  • Male
 

Citation

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Kang, J., Hu, J., Karra, R., Dickson, A. L., Tornini, V. A., Nachtrab, G., … Poss, K. D. (2016). Modulation of tissue repair by regeneration enhancer elements. Nature, 532(7598), 201–206. https://doi.org/10.1038/nature17644
Kang, Junsu, Jianxin Hu, Ravi Karra, Amy L. Dickson, Valerie A. Tornini, Gregory Nachtrab, Matthew Gemberling, Joseph A. Goldman, Brian L. Black, and Kenneth D. Poss. “Modulation of tissue repair by regeneration enhancer elements.Nature 532, no. 7598 (April 14, 2016): 201–6. https://doi.org/10.1038/nature17644.
Kang J, Hu J, Karra R, Dickson AL, Tornini VA, Nachtrab G, et al. Modulation of tissue repair by regeneration enhancer elements. Nature. 2016 Apr 14;532(7598):201–6.
Kang, Junsu, et al. “Modulation of tissue repair by regeneration enhancer elements.Nature, vol. 532, no. 7598, Apr. 2016, pp. 201–06. Pubmed, doi:10.1038/nature17644.
Kang J, Hu J, Karra R, Dickson AL, Tornini VA, Nachtrab G, Gemberling M, Goldman JA, Black BL, Poss KD. Modulation of tissue repair by regeneration enhancer elements. Nature. 2016 Apr 14;532(7598):201–206.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

April 14, 2016

Volume

532

Issue

7598

Start / End Page

201 / 206

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Wound Healing
  • Transgenes
  • Regeneration
  • Promoter Regions, Genetic
  • Organ Specificity
  • Myocytes, Cardiac
  • Mice
  • Male