| RRC ID |
73135
|
| 著者 |
Suzuki N, Kanai A, Suzuki Y, Ogino H, Ochi H.
|
| タイトル |
Adrenergic receptor signaling induced by Klf15, a regulator of regeneration enhancer, promotes kidney reconstruction.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
Despite the recent discovery of tissue regeneration enhancers in highly regenerative animals, upstream and downstream genetic programs connected by these enhancers still remain unclear. Here, we performed a genome-wide analysis of enhancers and associated genes in regenerating nephric tubules of Xenopus laevis. Putative enhancers were identified using assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) analyses. Their target genes were predicted based on their proximity to enhancers on genomic DNA and consistency of their transcriptome profiles to ATAC-seq/ChIP-seq profiles of the enhancers. Motif enrichment analysis identified the central role of Krüppel-like factors (Klf) in the enhancer. Klf15, a member of the Klf family, directly binds enhancers and stimulates expression of regenerative genes, including adrenoreceptor alpha 1A (adra1a), whereas inhibition of Klf15 activity results in failure of nephric tubule regeneration. Moreover, pharmacological inhibition of Adra1a-signaling suppresses nephric tubule regeneration, while its activation promotes nephric tubule regeneration and restores organ size. These results indicate that Klf15-dependent adrenergic receptor signaling through regeneration enhancers plays a central role in the genetic network for kidney regeneration.
|
| 巻・号 |
119(33)
|
| ページ |
e2204338119
|
| 公開日 |
2022-8-16
|
| DOI |
10.1073/pnas.2204338119
|
| PMID |
35939709
|
| PMC |
PMC9388080
|
| MeSH |
Animals
Chromatin / metabolism
Enhancer Elements, Genetic*
Gene Expression Regulation
Gene Regulatory Networks
Kidney Tubules* / physiology
Kruppel-Like Transcription Factors* / genetics
Kruppel-Like Transcription Factors* / metabolism
Receptors, Adrenergic* / metabolism
Regeneration* / genetics
Xenopus laevis
|
| IF |
9.412
|
| リソース情報 |
| ツメガエル・イモリ |
Xenopus tropicalis |
