Human glycosaminoglycan glucuronyltransferase I gene and a related processed pseudogene: genomic structure, chromosomal mapping and characterization

Here we describe the characterization of the human glycosaminoglycan glucur onyltransferase I gene (GlcAT-I) and a related pseudogene. The GlcAT-I gene was localized to human chromosome 11q12-q13 by in situ hybridization of me taphase chromosomes. GlcAT-I spanned 7 kb of human genomic DNA and was divi ded into five exons. Northern blot analysis showed that GlcAT-I exhibited u biquitous but markedly different expressions in the human tissues examined. The GlcAT-I promoter was approx. 3-fold more active in a melanoma cell lin e than in a hepatoma cell line, providing evidence for the differential reg ulation of the gene's expression. Stepwise 5` deletions of the promoter ide ntified a strong enhancer element between -303 and -153 by that included bi nding motifs for Ets, CREB (CAMP-response-element-binding protein) and STAT (signal transducers and activators of transcription). Screening of a human genomic library identified one additional distinct genomic clone containin g an approx. 1.4 kb sequence region that shared an overall 95.3 % nucleotid e identity with exons 1-5 of GlcAT-I However, a lack of intron sequences, a s well as the presence of several nucleotide mutations, insertions and dele tions that disrupted the potential GlcAT-I reading frame, suggested that th e clone contained a processed pseudogene. The pseudogene was localized to c hromosome 3. The human genome therefore contains two related GlcAT-I genes that are located on separate chromosomes.