The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Genomics Meets Glycomics—The First GWAS Study of Human N-Glycome Identifies HNF1α as a Master Regulator of Plasma Protein Fucosylation
Open accessAbstract
Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate their assembly are poorly understood. A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1α and its downstream target HNF4α regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1α is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1α as a master transcriptional regulator of multiple stages in the fucosylation process. This mechanism has implications for the regulation of immunity, embryonic development, and protein folding, as well as for our understanding of the molecular mechanisms underlying cancer, coronary heart disease, and metabolic and inflammatory disorders.
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Cites
GenABEL: an R library for genome-wide association analysis
Aulchenko, Y. S., Ripke, S., Isaacs, A., & van Duijn, C. M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm108 · Cited by 1,836 · cited 2×
“statistical software [53] was used for the association test under an”
MethodCycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins
Hart, G. W., Housley, M. P., & Slawson, C. (2007) · Nature · doi:10.1038/nature05815 · Cited by 1,418
Tissue-specific transcriptional regulation has diverged significantly between human and mouse
Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., & Fraenkel, E. (2007) · Nature Genetics · doi:10.1038/ng2047 · Cited by 506
New susceptibility locus for coronary artery disease on chromosome 3q22.3
Italian Atherosclerosis, T., Erdmann, J., Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Cardiogenics Consortium, Großhennig, A., Braund, P. S., König, I. R., Hengstenberg, C., Hall, A. S., et al. (2009) · Nature Genetics · doi:10.1038/ng.307 · Cited by 484 · cited 1×
“The possible function(s) of HNF1a are a focus of intense current interest following its recently reported associations in GWAS with plasma C-reactive protein (CRP) [27], gamma-glutamyl transferase (GGT) [28], LDL cholesterol and apolipoprotein [29,31] and coronary artery disease [29,46].”
BackgroundHandbook of Glycosyltransferases and Related Genes
(2014) · doi:10.1007/978-4-431-54240-7 · Cited by 318
Adaptive Regulation at the Cell Surface by N ‐Glycosylation
Dennis, J. W., Lau, K. S., Demetriou, M., & Nabi, I. R. (2009) · Traffic · doi:10.1111/j.1600-0854.2009.00981.x · Cited by 219
Cited by
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
Study, L. C., Köttgen, A., CARDIoGRAM Consortium, DIAGRAM Consortium, ICBP Consortium, MAGIC Consortium, Albrecht, E., Teumer, A., Vitart, V., Krumsiek, J., et al. (2013) · Nature Genetics · doi:10.1038/ng.2500 · Cited by 836
Self-citationGlycans Are a Novel Biomarker of Chronological and Biological Ages
Krištić, J., Vučković, F., Menni, C., Klarić, L., Keser, T., Beceheli, I., Pučić-Baković, M., Novokmet, M., Mangino, M., Thaqi, K., et al. (2014) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glt190 · Cited by 400
Self-citationLauc, G., Huffman, J. E., Pučić, M., Zgaga, L., Adamczyk, B., Mužinić, A., Novokmet, M., Polašek, O., Gornik, O., Krištić, J., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003225 · Cited by 361
Self-citationIntestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD
Kudelka, M. R., Stowell, S. R., Cummings, R. D., & Neish, A. S. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0331-7 · Cited by 355
High-sensitivity Analytical Approaches for the Structural Characterization of Glycoproteins
Alley, W. R., Mann, B. F., & Novotny, M. V. (2013) · Chemical Reviews · doi:10.1021/cr3003714 · Cited by 310
Metadata
- Authors
- Lauc, G., Essafi, A., Huffman, J. E., Hayward, C., Knežević, A., Kattla, J. J., Polašek, O., Gornik, O., Vitart, V., Abrahams, J. L., Pučić, M., Novokmet, M., Redžić, I., Campbell, S., Wild, S. H., Borovečki, F., Wang, W., Kolčić, I., Zgaga, L., Gyllensten, U., Wilson, J. F., Wright, A. F., Hastie, N. D., Campbell, H., Rudd, P. M., & Rudan, I.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-12-23
- Volume
- 6
- Issue
- 12
- Pages
- e1001256
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W2104785679
- Cited by
- 244
- References
- 6
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- gold
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- Lauc, G., Essafi, A., Huffman, J. E., Hayward, C., Knežević, A., Kattla, J. J., Polašek, O., Gornik, O., Vitart, V., Abrahams, J. L., Pučić, M., Novokmet, M., Redžić, I., Campbell, S., Wild, S. H., Borovečki, F., Wang, W., Kolčić, I., Zgaga, L., . . . Rudan, I. (2010). Genomics Meets Glycomics—The First GWAS Study of Human N-Glycome Identifies HNF1α as a Master Regulator of Plasma Protein Fucosylation. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1001256
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