Multiple transcription initiation and alternative splicing in the 5� untranslated region of the core 2 β1-6 N-acetylglucosaminyltransferase I gene

Abstract

The glycosyltransferase core 2 β1,6 N-acetylglucosaminyltransferase I (C2GnT I) plays an important regulatory role in the synthesis of biologically significant oligosaccharide structures. This gene is expressed in a variety of cell types, including lymphocytes and mucin-producing cells. The expression pattern of this gene suggests a complex system of regulation. To investigate the molecular regulation of this gene and locate potential promoter elements, rapid amplification of cDNA ends (RACE) analysis was used to determine the 5� ends of the C2GnT I mRNAs from a number of tissues. These experiments identified five C2GnT I mRNAs that are different in their 5� untranslated regions. The RACE cDNAs had four different 5� terminal sequences (exons A, B, D, and E'), suggesting four transcription initiation sites. One mRNA form was the result of alternative exon (exon C) utilization. These exons are spread across 60 kb of DNA on human chromosome 9, and all splice to the exon (exon F) that contains the C2GnT I coding region. Reverse transcription polymerase chain reaction experiments using primers specific for each of the four 5� end exon sequences revealed that the 5� terminal exons are differentially expressed, suggesting tissue specificity for the different 5� untranslated regions. These findings are consistent with the presence of multiple tissue-specific promoters for the C2GnT I gene. © Oxford University Press 2001.