Same role but different actors: genetic regulation of post-translational modification of two distinct proteins
Same role but different actors: genetic regulation of post-translational modification of two distinct proteins
Post-translational modifications (PTMs) diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare for the first time the genetic regulation of the same PTM of two proteins – glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identified 10 significantly associated loci, all novel. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1) as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. We propose that they affect the binding of different transcription factors in different tissues, with fucosylation of IgG being regulated by IKZF1 in B-cells and of transferrin by HNF1A in liver.
Vu?kovi? Frano、Sharapov Sodbo Z.、Navarro Pau、Pola?ek Ozren、Petrovic Tea、Vilaj Marija、Lauc Gordan、Landini Arianna、Hayward Caroline、Tsepilov Yakov A.、Klari? Lucija、Aulchenko Yurii S.、Wilson James F.、Trbojevi?-Akma?i? Irena
Genos Glycoscience Research LaboratoryLaboratory of Glycogenomics, Institute of Cytology and GeneticsMRC Human Genetics Unit, Institute for Genetics and Cancer, University of EdinburghDepartment of Public Health, School of Medicine, University of Split||Gen-info Ltd.Genos Glycoscience Research LaboratoryGenos Glycoscience Research LaboratoryGenos Glycoscience Research Laboratory||Faculty of Pharmacy and Biochemistry, University of ZagrebCentre for Global Health Research, Usher Institute, University of EdinburghMRC Human Genetics Unit, Institute for Genetics and Cancer, University of EdinburghLaboratory of Glycogenomics, Institute of Cytology and Genetics||Laboratory of Theoretical and Applied Functional Genomics, Novosibirsk State UniversityMRC Human Genetics Unit, Institute for Genetics and Cancer, University of EdinburghLaboratory of Glycogenomics, Institute of Cytology and GeneticsCentre for Global Health Research, Usher Institute, University of Edinburgh||MRC Human Genetics Unit, Institute for Genetics and Cancer, University of EdinburghGenos Glycoscience Research Laboratory
基础医学遗传学生物化学
Vu?kovi? Frano,Sharapov Sodbo Z.,Navarro Pau,Pola?ek Ozren,Petrovic Tea,Vilaj Marija,Lauc Gordan,Landini Arianna,Hayward Caroline,Tsepilov Yakov A.,Klari? Lucija,Aulchenko Yurii S.,Wilson James F.,Trbojevi?-Akma?i? Irena.Same role but different actors: genetic regulation of post-translational modification of two distinct proteins[EB/OL].(2025-03-28)[2025-05-14].https://www.biorxiv.org/content/10.1101/2021.05.04.442584.点此复制
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