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ZBED6 regulates Igf...
ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression
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- Naboulsi, Rakan (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Larsson, Mårten (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Andersson, Leif (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Swedish Univ Agr Sci, Dept Anim Breeding & Genet, S-75007 Uppsala, Sweden.;Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA.,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics,Uppsala University,Texas A&M University
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- Younis, Shady (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Ain Shams Univ, Dept Anim Breeding & Genet, Cairo 11241, Egypt.;Stanford Univ, Dept Med, Div Immunol & Rheumatol, Stanford, CA 94305 USA.
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(creator_code:org_t)
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- 2021-09-30
- 2021
- Engelska.
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://pub.epsilon.... (primary) (Raw object) (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
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