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Publication : A domesticated transposon mediates the effects of a single-nucleotide polymorphism responsible for enhanced muscle growth.

First Author  Butter F Year  2010
Journal  EMBO Rep Volume  11
Issue  4 Pages  305-11
PubMed ID  20134481 Mgi Jnum  J:160205
Mgi Id  MGI:4453828 Doi  10.1038/embor.2010.6
Citation  Butter F, et al. (2010) A domesticated transposon mediates the effects of a single-nucleotide polymorphism responsible for enhanced muscle growth. EMBO Rep 11(4):305-11
abstractText  Single-nucleotide polymorphisms (SNPs) in the regulatory regions of the genome can have a profound impact on phenotype. The G3072A polymorphism in intron 3 of insulin-like growth factor 2 (IGF2) is implicated in higher muscle content and reduced fat in European pigs and is bound by a putative repressor. Here, we identify this repressor--which we call muscle growth regulator (MGR)--by using a DNA protein interaction screen based on quantitative mass spectrometry. MGR has a bipartite nuclear localization signal, two BED-type zinc fingers and is highly conserved between placental mammals. Surprisingly, the gene is located in an intron and belongs to the hobo-Ac-Tam3 transposase superfamily, suggesting regulatory use of a formerly parasitic element. In transactivation assays, MGR differentially represses the expression of the two SNP variants. Knockdown of MGR in C2C12 myoblast cells upregulates Igf2 expression and mild overexpression retards growth. Thus, MGR is the repressor responsible for enhanced muscle growth in the IGF2 G3072A polymorphism in commercially bred pigs.
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