%0 Journal Article %A Nicola L. Stevenson %A Dylan J. M. Bergen %A Roderick E. H. Skinner %A Kate A. Robson Brown %A Chrissy L. Hammond %A David J. Stephens %T Giantin knockout models reveal the capacity of the Golgi to regulate its biochemistry by controlling glycosyltransferase expression %D 2017 %R 10.1101/123547 %J bioRxiv %P 123547 %X The Golgi is the cellular hub for glycosylation, controlling accurate processing of complex proteoglycans and glycolipids. Its structure and organisation is dependent on golgins which tether cisternal membranes and incoming transport vesicles. Here we show that knockout of the largest golgin, giantin, leads to substantial changes in gene expression despite only limited effects on Golgi structure. Notably, 22 Golgi-resident glycosyltransferases, but not glycan processing enzymes or the ER glycosylation machinery, are differentially expressed following giantin ablation. Most of these glycosyltransferases are highly downregulated following genetic knockout of giantin, including a near-complete loss of expression of GALNT3 in both mammalian cell and zebrafish models. Furthermore, knockout zebrafish exhibit increased bone mass density, hyperostosis, and ectopic calcium deposits recapitulating phenotypes of hyperphosphatemic familial tumoral calcinosis, a disease caused by mutations in GALNT3. Our data reveal a new feature of Golgi homeostasis, the ability to regulate glycosyltransferase expression to generate a functional proteoglycome. %U https://www.biorxiv.org/content/biorxiv/early/2017/04/03/123547.full.pdf