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Genomics meets glycomics - The first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation


Lauc, Gordan; Essafi, Abdelkader; Huffman, Jennifer E.; Hayward, Caroline; Knežević, Ana; Kattla, Jayesh J.; Polašek, Ozren; Gornik, Olga; Vitart, Veronique; Abrahams, Jodie L. et al.
Genomics meets glycomics - The first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation // Plos genetics, 6 (2010), 12; e1001256-1 doi:10.1371/journal.pgen.1001256 (međunarodna recenzija, članak, znanstveni)


Naslov
Genomics meets glycomics - The first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation

Autori
Lauc, Gordan ; Essafi, Abdelkader ; Huffman, Jennifer E. ; Hayward, Caroline ; Knežević, Ana ; Kattla, Jayesh J. ; Polašek, Ozren ; Gornik, Olga ; Vitart, Veronique ; Abrahams, Jodie L. ; Pučić, Maja ; Novokmet, Mislav ; Redžić, Irma ; Campbell, Susan ; Wild, Sarah H. ; Borovečki, Fran ; Wang, Wei ; Kolčić, Ivana ; Zgaga, Lina ; Gyllensten, Ulf ; Wilson, James F. ; Wright, Alan F. ; Hastie, Nicholas D. ; Campbell, Harry ; Rudd, Pauline ; Rudan, Igor

Izvornik
Plos genetics (1553-7390) 6 (2010), 12; E1001256-1

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
N-glycans; genome-wide association study

Sažetak
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 1a (HNF1a) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1a and its downstream target HNF4a regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1a is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1a 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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Javno zdravstvo i zdravstvena zaštita



POVEZANOST RADA


Projekt / tema
108-1081874-1923 - Genomska analiza transkriptoma i interaktoma u bolesnika s kompleksnim bolestima (Fran Borovečki, )
216-1080315-0302 - Odrednice zdravlja i bolesti u općoj i izoliranim ljudskim populacijama (Ozren Polašek, )
309-0061194-2023 - Glikoproteomika stresa i bolesti povezanih sa stresom (Gordan Lauc, )

Ustanove
Farmaceutsko-biokemijski fakultet, Zagreb,
Medicinski fakultet, Split,
GENOS d.o.o.

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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