Sachinandan De

Publications (2)11.45 Total impact

• Source

  Available from: Fredrik Pontén

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

  Ellen Markljung, Lin Jiang, Jacob D Jaffe, Tarjei S Mikkelsen, Ola Wallerman, Martin Larhammar, Xiaolan Zhang, Li Wang, Veronica Saenz-Vash, Andreas Gnirke, [......], Fredrik Pontén, Eric S Lander, Steven A Carr, Juleen R Zierath, Klas Kullander, Claes Wadelius, Kerstin Lindblad-Toh, Göran Andersson, Göran Hjälm, Leif Andersson
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  ABSTRACT: 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.
  PLoS Biology 12/2009; 7(12):e1000256. · 11.45 Impact Factor
• Article: ZBED6, a Novel Transcription Factor Derived from a Domesticated DNA Transposon Regulates IGF2 Expression and Muscle Growth

  Eric S Lander, Leif Andersson, Goran Hjalm, Goran Andersson, Kerstin Lindblad-Toh, Claes Wadelius, Klas Kullander, Juleen R Zierath, Fredrik Ponten, Sachinandan De, [......], Veronica Saenz-Vash, Li Wang, Xiaolan Zhang, Martin Larhammar, Ola Wallerman, Tarjei S Mikkelsen, Jacob D Jaffe, Lin Jiang, Ellen Markljung, Steven A Carr
  [show abstract] [hide abstract]
  ABSTRACT: A single nucleotide substitution in intron 3 of IGF2 in pigs abrogates a binding site for a repressor and leads to a 3-fold upregulation 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. National Human Genome Research Institute (U.S.) Knut and Alice Wallenberg Foundation Swedish Research Council Forskningsrådet för miljö, areella näringar och samhällsbyggande Fondation pour la recherche stratégique (France)
  PLoS.