PUBLICATION
Decoding an Organ Regeneration Switch by Dissecting Cardiac Regeneration Enhancers
- Authors
- Begeman, I.J., Shin, K., Osorio-Méndez, D., Kurth, A., Lee, N., Chamberlain, T.J., Pelegri, F.J., Kang, J.
- ID
- ZDB-PUB-201130-3
- Date
- 2020
- Source
- Development (Cambridge, England) 147(24): (Journal)
- Registered Authors
- Kang, Junsu, Lee, Nutishia, Pelegri, Francisco
- Keywords
- Enhancer, Gene expression, Heart, Injury, Regeneration, Zebrafish
- MeSH Terms
-
- Animals
- Enhancer Elements, Genetic*
- Gene Expression Regulation
- Gene Expression Regulation, Developmental/genetics
- Heart/growth & development*
- Heart Injuries/genetics*
- Heart Injuries/pathology
- Heart Injuries/rehabilitation
- Humans
- Organogenesis/genetics
- Regeneration/genetics*
- Regeneration/physiology
- Wound Healing/genetics
- Wound Healing/physiology
- Zebrafish/genetics
- Zebrafish/growth & development
- PubMed
- 33246928 Full text @ Development
Citation
Begeman, I.J., Shin, K., Osorio-Méndez, D., Kurth, A., Lee, N., Chamberlain, T.J., Pelegri, F.J., Kang, J. (2020) Decoding an Organ Regeneration Switch by Dissecting Cardiac Regeneration Enhancers. Development (Cambridge, England). 147(24):.
Abstract
Heart regeneration in regeneration-competent organisms can be accomplished through the remodeling of gene expression in response to cardiac injury. This dynamic transcriptional response relies on the activities of tissue regeneration enhancer elements (TREEs); however, the mechanisms underlying TREEs are poorly understood. We dissected a cardiac regeneration enhancer in zebrafish to elucidate the mechanisms governing spatiotemporal gene expression during heart regeneration. Cardiac lepb regeneration enhancer (cLEN) exhibits dynamic, regeneration-dependent activity in the heart. We found that multiple injury-activated regulatory elements are distributed throughout the enhancer region. This analysis also revealed that cardiac regeneration enhancers are not only activated by injury, but surprisingly, they are also actively repressed in the absence of injury. Our data identified a short 22-bp DNA element containing a key repressive element. Comparative analysis across Danio species indicated that the repressive element is conserved in closely related species. The repression mechanism is not operational during embryogenesis and emerges when the heart begins to mature. Incorporating both activation and repression components into the mechanism of tissue regeneration constitutes a new paradigm that may be extrapolated to other regeneration scenarios.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping