TY - JOUR
T1 - Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates
AU - Wang, Wei
AU - Hu, Chi Kuo
AU - Zeng, An
AU - Alegre, Dana
AU - Hu, Deqing
AU - Gotting, Kirsten
AU - Granillo, Augusto Ortega
AU - Wang, Yongfu
AU - Robb, Sofia
AU - Schnittker, Robert
AU - Zhang, Shasha
AU - Alegre, Dillon
AU - Li, Hua
AU - Ross, Eric
AU - Zhang, Ning
AU - Brunet, Anne
AU - Alvarado, Alejandro Sánchez
N1 - Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85090320119
U2 - 10.1126/SCIENCE.AAZ3090
DO - 10.1126/SCIENCE.AAZ3090
M3 - Article
C2 - 32883834
AN - SCOPUS:85090320119
SN - 0036-8075
VL - 369
JO - Science
JF - Science
IS - 6508
M1 - eaaz3090
ER -