Organization of the beta-galactoside alpha 2,6-sialyltransferase gene. Evidence for the transcriptional regulation of terminal glycosylation.
Little is currently known about the mechanisms by which the cellular glycosylation machinery is regulated to produce cell type-specific glycosylation sequences on glycoprotein and glycolipid sugar chains. Previously, we have shown that one enzyme involved in terminal glycosylation, beta-galactoside alpha 2,6-sialyltransferase, is expressed in a tissue-specific fashion, with the highest enzyme activity as well as mRNA levels being found in the liver. In addition, the liver mRNA was found to be 4.3 kilobases (kb) in size as compared to a larger message of 4.7 kb in other tissues. To understand the cellular regulation of expression of this sialyltransferase, we have cloned the rat gene encoding the 4.3-kb liver mRNA and found that it spans 40 kb of genomic DNA and contains 6 exons. The gene was found to be very similar in size and exon organization to the murine beta 1,4-galactosyltransferase gene, even though this enzyme has no sequence homology to alpha 2,6-sialyltransferase. The promoter responsible for the production of the liver alpha 2,6-sialyltransferase mRNA is approximately 50-fold more active in a hepatoma cell line known to express this enzyme (HepG2) than in a cell line shown not to express this enzyme (Chinese hamster ovary) and contains consensus binding sites for the liver restricted transcription factors HNF-1 and DBP as well as the transcription factors AP-1 and AP-2. These observations are in accord with the restricted expression of the 4.3-kb mRNA, and provides evidence for the cellular regulation of glycosylation at the level of transcription.
Svensson
E C
EC
Department of Biological Chemistry, UCLA School of Medicine 90024.
Soreghan
B
B
Paulson
J C
JC
D000818:Animals; D001483:Base Sequence; D003360:Cosmids; D005786:Gene Expression Regulation; D015723:Gene Library; D005796:Genes; D006031:Glycosylation; D007438:Introns; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015183:Restriction Mapping; D012799:Sialyltransferases / Q000235:genetics*; D014158:Transcription, Genetic; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D012333:RNA, Messenger; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase