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ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression

Naboulsi, Rakan and Larsson, Marten and Andersson, Leif and Younis, Shady (2021). ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression. Scientific Reports. 11 , 19484
[Research article]

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Abstract

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.

Authors/Creators:Naboulsi, Rakan and Larsson, Marten and Andersson, Leif and Younis, Shady
Title:ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression
Series Name/Journal:Scientific Reports
Year of publishing :2021
Volume:11
Article number:19484
Number of Pages:12
Publisher:NATURE PORTFOLIO
ISSN:2045-2322
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Developmental Biology
URN:NBN:urn:nbn:se:slu:epsilon-p-114071
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-114071
Additional ID:
Type of IDID
DOI10.1038/s41598-021-98777-0
Web of Science (WoS)000702737500110
ID Code:25955
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:26 Oct 2021 13:25
Metadata Last Modified:26 Oct 2021 13:31

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