Research Paper Volume 15, Issue 24 pp 14509—14552
Mapping of the gene network that regulates glycan clock of ageing
Figure 3. A graphical review of up-to-date functional validation of GWAS hits associated with IgG glycosylation using HEK293FS transient expression system with stably integrated dCas9-VPR or dCas9-KRAB fusions. When specific gRNA targeted dCas9-VPR to two estrogen associated genes, RUNX3 and SPINK4 (Mijakovac et al. 2021), as well as to the TNFRSF13B, MANBA and EEF1A1 loci, transcription was upregulated that resulted in decreased levels of galactosylated (red arrow within box), increased levels of agalactosylated IgG glycan structures (green arrow within box) or both. Downregulated transcription of SPPL3 resulted in an increase in galactosylated structures with a concomitant decrease in agalactosylated IgG glycan structures. Protein structures do not depict true protein structures in humans, generic protein shapes are chosen for easier visualization. Figure was created with BioRender.com. Accessed on 16 November 2021.