Edinburgh Research Explorer

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

Research output: Contribution to journalArticle

  • Gordan Lauc
  • Jennifer E. Huffman
  • Ana Knezevic
  • Jayesh J. Kattla
  • Ozren Polasek
  • Olga Gornik
  • Jodie L. Abrahams
  • Maja Pucic
  • Mislav Novokmet
  • Irma Redzic
  • Susan Campbell
  • Fran Borovecki
  • Wei Wang
  • Ivana Kolcic
  • Ulf Gyllensten
  • Pauline M. Rudd

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Rights statement: Copyright: © 2010 Lauc et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Final published version, 1.8 MB, PDF document

http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1001256
Original languageEnglish
Article numbere1001256
Pages (from-to)-
Number of pages14
JournalPLoS Genetics
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2010

Abstract

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.

Download statistics

No data available

ID: 3022073