Epigenetic regulation of HNF1A expression associates with changes in the composition of the human plasma N-glycome (CROSBI ID 587447)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Zoldoš, Vlatka ; Horvat, Tomislav ; Knežević, Ana ; McCarthy, Mark I ; Huffman, Jennifer E ; Polašek, Ozren ; Rudan, Igor ; Herceg, Zdenko ; Lauc, Gordan
engleski
Epigenetic regulation of HNF1A expression associates with changes in the composition of the human plasma N-glycome
Protein glycosylation is an ubiquitous modification which affects protein structure and function. In a recent genome wide association study (GWAS) we identified transcription factor HNF1A as an important regulator of plasma protein N-glycosylation. To evaluate the potential impact of epigenetic regulation of HNF1A on protein N-glycosylation we quantified CpG methylation level in 810 individuals by pyrosequencing of bisulfate converted HNF1A gene and then correlated the DNA methylation levels to the composition of plasma and IgG N-glycomes. To verify that the methylation level at chosen CpG sites reflects the HNF1A expression level we analyzed the two and compared between the different hepatocellular carcinoma cell lines and the cell lines of other origins. The most significant association between the level of HNF1A methylation and plasma N-glycans appeared at the level of branched N-glycan structures, while there were no significant associations with IgG glycans. The indication that inactivation of HNF1A promotes glycan branching was supported by the analysis of plasma N-glycomes in patients with inactivating mutations in HNF1A, where the increase in plasma glycan branching was observed as well. This study represents the first demonstration of epigenetic regulation of plasma N-glycome composition, suggesting potential mechanism by which epigenetic deregulation of the glycome may contribute to disease development.
epigenetics; CpG methylation; HNF1A expression; N-glycome; MODY3
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Podaci o prilogu
57-57.
2012.
objavljeno
Podaci o matičnoj publikaciji
Book of abstracts, 3rd Congress of Croatian geneticists with international participation
Franekić, Jasna ; Garaj-Vrhovac, Verica
Sveti Ivan Zelina:
978-953-57128-0-0
Podaci o skupu
3rd Congress of Croatian Geneticists with international participation
predavanje
13.05.2012-16.05.2012
Krk, Otok Krk, Hrvatska