Research article - Peer-reviewed, 2021
ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression
Naboulsi, Rakan; Larsson, Marten; Andersson, Leif; Younis, ShadyAbstract
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.Published in
Scientific Reports2021, volume: 11, number: 1, article number: 19484
Publisher: NATURE PORTFOLIO
Authors' information
Naboulsi, Rakan
Uppsala University
Larsson, Marten
Uppsala University
Andersson, Leif
Uppsala University
Andersson, Leif
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Andersson, Leif
Texas A&M University
Younis, Shady
Stanford University
Younis, Shady
Ain Shams University
Younis, Shady
Uppsala University
UKÄ Subject classification
Developmental Biology
Publication Identifiers
DOI: https://doi.org/10.1038/s41598-021-98777-0
URI (permanent link to this page)
https://res.slu.se/id/publ/114071