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Pregled bibliografske jedinice broj: 496268

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, 14 doi:10.1371/journal.pgen.1001256 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 496268 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

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, 14

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


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

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

Poveznice na cjeloviti tekst rada:

doi journals.plos.org

Citiraj ovu publikaciju:

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, 14 doi:10.1371/journal.pgen.1001256 (međunarodna recenzija, članak, znanstveni)
Lauc, G., Essafi, A., Huffman, J., Hayward, C., Knežević, A., Kattla, J., Polašek, O., Gornik, O., Vitart, V. & Abrahams, J. (2010) Genomics meets glycomics - The first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation. PLOS genetics, 6 (12), e1001256, 14 doi:10.1371/journal.pgen.1001256.
@article{article, author = {Lauc, Gordan and Essafi, Abdelkader and Huffman, Jennifer E. and Hayward, Caroline and Kne\v{z}evi\'{c}, Ana and Kattla, Jayesh J. and Pola\v{s}ek, Ozren and Gornik, Olga and Vitart, Veronique and Abrahams, Jodie L. and Pu\v{c}i\'{c}, Maja and Novokmet, Mislav and Red\v{z}i\'{c}, Irma and Campbell, Susan and Wild, Sarah H. and Borove\v{c}ki, Fran and Wang, Wei and Kol\v{c}i\'{c}, Ivana and Zgaga, Lina and Gyllensten, Ulf and Wilson, James F. and Wright, Alan F. and Hastie, Nicholas D. and Campbell, Harry and Rudd, Pauline and Rudan, Igor}, year = {2010}, pages = {14}, DOI = {10.1371/journal.pgen.1001256}, chapter = {e1001256}, keywords = {N-glycans, genome-wide association study}, journal = {PLOS genetics}, doi = {10.1371/journal.pgen.1001256}, volume = {6}, number = {12}, issn = {1553-7390}, title = {Genomics meets glycomics - The first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation}, keyword = {N-glycans, genome-wide association study}, chapternumber = {e1001256} }
@article{article, author = {Lauc, Gordan and Essafi, Abdelkader and Huffman, Jennifer E. and Hayward, Caroline and Kne\v{z}evi\'{c}, Ana and Kattla, Jayesh J. and Pola\v{s}ek, Ozren and Gornik, Olga and Vitart, Veronique and Abrahams, Jodie L. and Pu\v{c}i\'{c}, Maja and Novokmet, Mislav and Red\v{z}i\'{c}, Irma and Campbell, Susan and Wild, Sarah H. and Borove\v{c}ki, Fran and Wang, Wei and Kol\v{c}i\'{c}, Ivana and Zgaga, Lina and Gyllensten, Ulf and Wilson, James F. and Wright, Alan F. and Hastie, Nicholas D. and Campbell, Harry and Rudd, Pauline and Rudan, Igor}, year = {2010}, pages = {14}, DOI = {10.1371/journal.pgen.1001256}, chapter = {e1001256}, keywords = {N-glycans, genome-wide association study}, journal = {PLOS genetics}, doi = {10.1371/journal.pgen.1001256}, volume = {6}, number = {12}, issn = {1553-7390}, title = {Genomics meets glycomics - The first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation}, keyword = {N-glycans, genome-wide association study}, chapternumber = {e1001256} }

Časopis indeksira:


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


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