PUBLICATION

Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates

Authors
Wang, W., Hu, C.K., Zeng, A., Alegre, D., Hu, D., Gotting, K., Ortega Granillo, A., Wang, Y., Robb, S., Schnittker, R., Zhang, S., Alegre, D., Li, H., Ross, E., Zhang, N., Brunet, A., Sánchez Alvarado, A.
ID
ZDB-PUB-201215-18
Date
2020
Source
Science (New York, N.Y.)   369(6508): (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Transcriptional Activation
  • Killifishes/genetics*
  • Killifishes/physiology*
  • Regeneration/genetics*
  • Enhancer Elements, Genetic/physiology*
  • Epigenesis, Genetic
  • Transcription Factor AP-1/chemistry
  • Transcription Factor AP-1/metabolism
  • Single-Cell Analysis
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Histones/metabolism
  • Inhibin-beta Subunits/genetics
  • Evolution, Molecular*
  • Gene Expression Profiling
  • RNA-Seq
  • Amino Acid Motifs
PubMed
32883834 Full text @ Science
Abstract
Vertebrates vary in their ability to regenerate, and the genetic mechanisms underlying such disparity remain elusive. Comparative epigenomic profiling and single-cell sequencing of two related teleost fish uncovered species-specific and evolutionarily conserved genomic responses to regeneration. The conserved response revealed several regeneration-responsive enhancers (RREs), including an element upstream to inhibin beta A (inhba), a known effector of vertebrate regeneration. This element activated expression in regenerating transgenic fish, and its genomic deletion perturbed caudal fin regeneration and abrogated cardiac regeneration altogether. The enhancer is present in mammals, shares functionally essential activator protein 1 (AP-1)-binding motifs, and responds to injury, but it cannot rescue regeneration in fish. This work suggests that changes in AP-1-enriched RREs are likely a crucial source of loss of regenerative capacities in vertebrates.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping