Naslov
Epigenetic silencing of HNF1A associates with changes in the composition of the human plasma N-glycome

Autori
Horvat, Tomislav ; Knežević, Ana ; McCarthy, Mark I ; Rudan, Igor ; Herceg, Zdenko ; Lauc, Gordan ; Zoldoš, Vlatka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Program and Abstract Book of the Sixth Meeting on Chromatin Structure and Function. / Kouzarides, Tony - : Abcam, 2011

Skup
The sixth meeting on Chromatin Structure and Function

Mjesto i datum
Aruba, 05.12.2011. - 08.12.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
bisulphite sequencing; HNF1A; DNA methylation; N-glycosylation; transcription factor

Sažetak
Protein glycosylation is a ubiquitous modification which affects protein structure and function. Recent genome wide association study 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 glycosylation we quantified its CpG methylation in 810 individuals. Correlations between methylation of four CpG sites and the composition of plasma and IgG glycomes were analyzed. Several significant associations were observed between the level of HNF1A methylation and plasma N-glycans, the most significant one at the level of branched N-glycan structures, while there were no significant associations with IgG glycans. The hypothesis that inactivation of HNF1A promotes glycan branching was supported by the analysis of plasma N-glycomes in 61 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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA