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  • Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates.

Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates.

Science (New York, N.Y.) (2020-09-05)
Wei Wang, Chi-Kuo Hu, An Zeng, Dana Alegre, Deqing Hu, Kirsten Gotting, Augusto Ortega Granillo, Yongfu Wang, Sofia Robb, Robert Schnittker, Shasha Zhang, Dillon Alegre, Hua Li, Eric Ross, Ning Zhang, Anne Brunet, Alejandro Sánchez Alvarado
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.

MATERIALS
Product Number
Brand
Product Description

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Orange G, certified by the Biological Stain Commission
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Phosphomolybdic acid hydrate, ACS reagent
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Acid Fuchsin, used in tissue staining
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Bouin′s solution, histological fixative
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Xylenes, histological grade