English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The expression of  Igf2  in mammals shows a complex regulation involving multiple promoters and epigenetic mechanisms. We previously identified a novel regulatory mechanism based on the interaction between the transcriptional factor ZBED6 and  Igf2  intron. Disruption of the ZBED6- Igf2  interaction leads to a dramatic up-regulation of IGF2 expression postnatally. In the current study we characterize an additional layer of regulation involving  miR483  encoded by another  Igf2  intron. We found a highly significant up-regulation of  miR483  expression when the ZBED6- Igf2  axis is disrupted in transgenic mice. Furthermore, CRISPR/Cas9 mediated knock-out of  miR483  in C2C12 myoblast cells, both wild-type and cells with disrupted ZBED6- Igf2  axis ( Igf2  dGGCT ), resulted in down-regulation of  Igf2  expression and a reduced proliferation rate. This was further validated using  miR483  mimics and inhibitors. RNA-seq analysis revealed a significant enrichment of genes involved in the PI3K-Akt signaling pathway among genes down-regulated in  miR483  −/−  cells, including  Igf2  down-regulation. The opposite pattern was observed in  Igf2  dGGCT  cells, where  Igf2  is up-regulated. Our data suggest a positive feedback between  miR483  and  Igf2  promoter activity, strongly affecting how ZBED6 controls  Igf2  expression in various cell types.

ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression