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Elife 2019 Jan 08;8. doi: 10.7554/eLife.43186.
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Arid3a regulates nephric tubule regeneration via evolutionarily conserved regeneration signal-response enhancers.

Suzuki N , Hirano K , Ogino H , Ochi H .

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.

PubMed ID: 30616715
PMC ID: PMC6324879
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: arid3a arid3b h3-3a hnf1b hnf4a hsp70 kdm4a lhx1 myc nphs2 osr1 osr2 pax2 pax8 six2 spib
GO keywords: chromatin remodeling [+]
Antibodies: Arid3a Ab1 H3f3a Ab26 H3f3a Ab9 Myc Ab5
Morpholinos: arid3a MO2 arid3a MO3 photo MO

Article Images: [+] show captions
References [+] :
Andersson, An atlas of active enhancers across human cell types and tissues. 2014, Pubmed