Arid3a regulates nephric tubule regeneration via evolutionarily conserved regeneration signal-response enhancers

Elife. 2019 Jan 8;8:e43186. doi: 10.7554/eLife.43186.


Amphibians and fish have the ability to regenerate numerous tissues, whereas mammals have a limited regenerative capacity. Despite numerous developmental genes becoming reactivated during regeneration, an extensive analysis is yet to be performed on whether highly regenerative animals utilize unique cis-regulatory elements for the reactivation of genes during regeneration and how such cis-regulatory elements become activated. Here, we screened regeneration signal-response enhancers at the lhx1 locus using Xenopus and found that the noncoding elements conserved from fish to human function as enhancers in the regenerating nephric tubules. A DNA-binding motif of Arid3a, a component of H3K9me3 demethylases, was commonly found in RSREs. Arid3a binds to RSREs and reduces the H3K9me3 levels. It promotes cell cycle progression and causes the outgrowth of nephric tubules, whereas the conditional knockdown of arid3a using photo-morpholino inhibits regeneration. These results suggest that Arid3a contributes to the regeneration of nephric tubules by decreasing H3K9me3 on RSREs.

Keywords: Arid3a; H3K9me3; Xenopus laevis; developmental biology; nephric tubule; regeneration signal-response enhancer; transgenic enhancer screening; xenopus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biological Evolution*
  • Cell Cycle
  • Chromatin / metabolism
  • Conserved Sequence*
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic*
  • Fishes
  • Humans
  • Kidney Tubules / physiology*
  • Nephrectomy
  • Nephrons / physiology*
  • Regeneration / physiology*
  • Transcription Factors / metabolism*
  • Xenopus / physiology*
  • Xenopus Proteins / metabolism*


  • Arid3a protein, Xenopus
  • Chromatin
  • DNA-Binding Proteins
  • Transcription Factors
  • Xenopus Proteins