ZBED6, a Novel Transcription Factor Derived from a Domesticated DNA Transposon Regulates IGF2 Expression and Muscle Growth
Name
Markljung-2009-ZBED6, a Novel Transcription Factor Derived from a Domesticated DNA Transposon Regulates IGF2 Expression and Muscle Growth.pdf
Size
3.72 MB
Format
Adobe PDF
Checksum (MD5)
be49c5d1291736fa09d8f8662678ab67
Author(s)
Andersson, Leif
Hjalm, Goran
Andersson, Goran
Lindblad-Toh, Kerstin
Wadelius, Claes
Kullander, Klas
Zierath, Juleen R.
Ponten, Fredrik
De, Sachinandan
Stromberg, Sara
Date Issued
December 2009
Journal
PLoS Biology
Publisher
Public Library of Science
Citation
Markljung, Ellen et al. “ZBED6, a Novel Transcription Factor Derived from a Domesticated DNA Transposon Regulates IGF2 Expression and Muscle Growth.” PLoS Biol 7.12 (2009): e1000256. © 2009 Markljung et al.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
http://dx.doi.org/10.1371/journal.pbio.1000256
