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

EMBO Reports
Falk ButterMatthias Mann

Abstract

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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Citations

Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Xuan WangNils Welsh
Oct 13, 2010·The Journal of Biological Chemistry·Damir T AlzhanovPeter Rotwein
Feb 13, 2013·Briefings in Functional Genomics·Till BartkePeter A DiMaggio
Oct 19, 2012·American Journal of Physiology. Cell Physiology·Samantha GardnerPeter Rotwein
Jan 27, 2012·American Journal of Physiology. Renal Physiology·Eric T WeatherfordCurt D Sigmund
Aug 29, 2012·International Journal of Evolutionary Biology·Domitille ChalopinJean-Nicolas Volff
Nov 26, 2010·Molecular Endocrinology·Samantha GardnerPeter Rotwein
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Kristine J Kines, Victoria P Belancio
Oct 19, 2013·Human Genetics·Hendrik G Stunnenberg, Nina C Hubner
May 10, 2011·Annual Review of Biochemistry·Jürgen Cox, Matthias Mann
Jun 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Akhtar AliTobias Sjöblom
Sep 1, 2015·Nature Structural & Molecular Biology·Alfred G TamayoCharles J Weitz
Jun 12, 2013·American Journal of Human Genetics·Natalie R PowersJeffrey R Gruen
Feb 18, 2011·Transcription·Leif AnderssonElisabeth Sundström
Sep 26, 2013·Journal of Proteomics·A TachenyP Renard
Jul 13, 2016·Human Molecular Genetics·Michael Wierer, Matthias Mann
Feb 9, 2017·Nature Communications·Dennis KappeiFalk Butter
Mar 8, 2013·International Journal of Molecular Sciences·Monica SoldiTiziana Bonaldi
Oct 19, 2017·PLoS Pathogens·Deepa RajagopalanSudhakar Jha
Jun 5, 2010·Molecular BioSystems·Cornelia G SpruijtMichiel Vermeulen
Jun 20, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shady YounisLeif Andersson
Dec 10, 2015·Physiological Genomics·Damir Alzhanov, Peter Rotwein
Jan 19, 2011·Chembiochem : a European Journal of Chemical Biology·H Christian EberlMichiel Vermeulen
Mar 6, 2010·EMBO Reports·Jean-Nicolas Volff
Nov 3, 2017·Neuron·Fabian Hosp, Matthias Mann

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Methods Mentioned

BETA
pulldowns
electrophoretic mobility-shift assay
affinity purification
immunoprecipitation
transgenic
pulldown
electrophoresis
Assay
fluorescence-activated cell sorting
transfection

Software Mentioned

Multi Gauge
Ensembl genome browser
CoreBoost
Mascot

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