Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried 82152, Germany.
EMBO Rep. 2010 Apr;11(4):305-11. doi: 10.1038/embor.2010.6. Epub 2010 Feb 5.
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.
基因组调控区的单核苷酸多态性（SNPs）可能对表型产生深远影响。胰岛素样生长因子 2（IGF2）第 3 内含子中的 G3072A 多态性与欧洲猪的更高肌肉含量和更低脂肪含量有关，并且受到一个假定的抑制剂的束缚。在这里，我们通过基于定量质谱的 DNA 蛋白相互作用筛选来鉴定这种抑制剂 - 我们称之为肌肉生长调节剂（MGR）。MGR 具有二分核定位信号、两个 BED 型锌指，并且在胎盘哺乳动物之间高度保守。令人惊讶的是，该基因位于内含子中，属于 hobo-Ac-Tam3 转座酶超家族，表明以前寄生元件的调节使用。在转激活测定中，MGR 差异抑制两个 SNP 变体的表达。在 C2C12 成肌细胞中敲低 MGR 会上调 Igf2 表达，轻度过表达会减缓生长。因此，MGR 是负责商业养殖猪 IGF2 G3072A 多态性中增强肌肉生长的抑制剂。
