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ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth

Markljung, Ellen (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Jiang, Lin (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Jaffe, Jacob D. (author)
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Mikkelsen, Tarjei S. (author)
Wallerman, Ola (author)
Uppsala universitet,Institutionen för genetik och patologi
Larhammar, Martin (author)
Uppsala universitet,Genetisk utvecklingsbiologi
Zhang, Xiaolan (author)
Wang, Li (author)
Saenz-Vash, Veronica (author)
Gnirke, Andreas (author)
Lindroth, Anders (author)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics
Barrés, Romain (author)
Yan, Jie (author)
Karolinska Institutet
Strömberg, Sara (author)
Uppsala universitet,Institutionen för genetik och patologi
De, Sachinandan (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Pontén, Fredrik (author)
Uppsala universitet,Institutionen för genetik och patologi
Lander, Eric S. (author)
Carr, Steven A. (author)
Zierath, Juleen R. (author)
Karolinska Institutet
Kullander, Klas (author)
Uppsala universitet,Genetisk utvecklingsbiologi
Wadelius, Claes (author)
Uppsala universitet,Institutionen för genetik och patologi
Lindblad-Toh, Kerstin (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Andersson, Göran (author)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics
Hjälm, Göran (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Andersson, Leif (author)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics,Uppsala University
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 (creator_code:org_t)
 
2009-12-15
2009
English.
In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 7:12, s. e1000256-
Related links:
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • A single nucleotide substitution in intron 3 of IGF2 in pigs abrogates a binding site for a repressor and leads to a 3-fold up-regulation of IGF2 in skeletal muscle. The mutation has major effects on muscle growth, size of the heart, and fat deposition. Here, we have identified the repressor and find that the protein, named ZBED6, is previously unknown, specific for placental mammals, and derived from an exapted DNA transposon. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. Chromatin immunoprecipitation (ChIP) sequencing using C2C12 cells identified about 2,500 ZBED6 binding sites in the genome, and the deduced consensus motif gave a perfect match with the established binding site in Igf2. Genes associated with ZBED6 binding sites showed a highly significant enrichment for certain Gene Ontology classifications, including development and transcriptional regulation. The phenotypic effects in mutant pigs and ZBED6-silenced C2C12 myoblasts, the extreme sequence conservation, its nucleolar localization, the broad tissue distribution, and the many target genes with essential biological functions suggest that ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation, and growth.

Subject headings

LANTBRUKSVETENSKAPER  -- Veterinärmedicin (hsv//swe)
AGRICULTURAL SCIENCES  -- Veterinary Science (hsv//eng)

Keyword

MEDICINE
MEDICIN

Publication and Content Type

ref (subject category)
art (subject category)

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