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2016 ; 532
(7598
): 201-6
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Modulation of tissue repair by regeneration enhancer elements
#MMPMID27049946
Kang J
; Hu J
; Karra R
; Dickson AL
; Tornini VA
; Nachtrab G
; Gemberling M
; Goldman JA
; Black BL
; Poss KD
Nature
2016[Apr]; 532
(7598
): 201-6
PMID27049946
show ga
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.
|Acetylation
[MESH]
|Animal Fins/injuries/metabolism
[MESH]
|Animals
[MESH]
|Animals, Newborn
[MESH]
|Cell Proliferation
[MESH]
|Chromatin Assembly and Disassembly/genetics
[MESH]