Epigenetička regulacija gena BACH2 i njegova uloga u glikozilaciji imunoglobulina G

doctoral thesis

• Title (english): Epigenetic regulation of BACH2 gene and its role in IgG glycosylation
• Author: Marija Klasić
• Mentor: Vlatka Zoldoš (mentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Inga Marijanović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018-12-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

Cjelogenomskim studijama povezanosti gen BACH2 povezan je s upalnim bolestima crijeva (IBD, od engl. inflammatory bowel disease) i s N-glikozilacijom imunoglobulina G (IgG), efektorskom molekulom humoralne imunosti. Neodgovarajući imunosni odgovor na crijevnu mikrofloru u osoba s genetskom predispozicijom jedan je od uzroka IBD-a. S druge strane, različiti okolišni faktori kroz epigenetičke mehanizme sudjeluju u razvoju ove bolesti. Stoga je glavni cilj ovog istraživanja bio utvrditi ulogu gena BACH2 u N-glikozilaciji IgG-a, te u razvoju IBD-a. Analizirala sam CpG-metilaciju promotora ovoga gena u punoj krvi i B-limfocitima CD19+ IBD-pacijenata i zdravih ljudi, upotrebom bisulfitnog pirosekvenciranja. Kod pacijenata s Crohnovom bolesti utvrdila sam da dolazi do hipometilacije promotora gena BACH2. Također sam napravila analizu korelacije CpG-metilacije i glikana IgG-a istih ispitanika. Kako bih otkrila regulira li transkripcijski faktor BACH2 neke od glikoziltransferaza napravila sam kromatinsku imunoprecipitaciju na kandidat genima. Dobiveni rezultati upućuju na indirektnu ulogu BACH2 u glikozilaciji IgG-a, na mogući mehanizam regulacije ekspresije gena BACH2 i njegove povezanosti s IBD-om kroz promjenu metilacije DNA.

Abstract (english)

Genome-wide association studies connected BACH2 gene with inflammatory bowel disease (IBD) and N-glycosylation of immunoglobulin G (IgG), effector molecule of humoral immunity. Inappropriate immune response to intestinal microflora in genetically susceptible individuals is one cause of IBD. On the other hand, environmental factors are also important for disease development through epigenetic mechanisms. The main goal of this research was to determine the role of BACH2 in IgG N-glycosylation and IBD development. I analyzed BACH2 promoter methylation in blood and CD19+ B lymphocytes in IBD patients and healthy people, using bisulfite pyrosequencing. In Crohn’s disease patients, I found significant hypomethylation of BACH2 promoter. I also analyzed correlations of BACH2 methylation and IgG glycans of the same patients. To identify if BACH2 regulates genes encoding for glycosyltransferases, I performed chromatin immunoprecipitation on candidate genes. Described results indicate possible indirect role of BACH2 in IgG glycosylation, mechanism of BACH2 regulation and its association with IBD through DNA methylation changes.

• Keywords: metilacija DNA; histonske modifikacije; BACH2; imunoglobulin G; glikozilacija; upalne bolesti crijeva
• Keywords (english): DNA methylation; histone modifications; BACH2; immunoglobulin G; glycosylation; inflammatory bowel disease
• Language: croatian
• URN:NBN: urn:nbn:hr:217:074649
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2020-12-18
• Created on: 2019-01-15 09:08:21