A domesticated transposon mediates the effects of a single-nucleotide polymorphism responsible for enhanced muscle growth.
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.
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried 82152, Germany.
Falk
F
Butter
Dennis
D
Kappei
Frank
F
Buchholz
Michiel
M
Vermeulen
Matthias
M
Mann
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004251:DNA Transposable Elements / Q000235:genetics / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism*; D007438:Introns / Q000235:genetics; D051379:Mice; D009132:Muscles / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013552:Swine
D004251:DNA Transposable Elements; D012097:Repressor Proteins; D007335:Insulin-Like Growth Factor II