Molecular cloning, expression, and chromosomal mapping of human chondroitin 4-sulfotransferase, whose expression pattern in human tissues is different from that of chondroitin 6-sulfotransferase

Chondroitin 4-sulfotransferase (C4ST) catalyzes the transfer of sulfate fro m 3'-phosphoadenosine 5'-phosphosulfate to position 4 of the N-acetylgalact osamine residues of chondroitin, We previously reported the cloning of C4ST cDNA from mouse brain. We here report the cloning and expression of human C4ST cDNA The cDNA was isolated from a human fetal brain cDNA library by hy bridization with a DNA probe prepared from rat poly(A)(+) RNA used for the cloning of mouse C4ST cDNA The cDNA comprises a single open reading frame t hat predicts a Type II transmembrane protein composed of 352 amino acids. T he protein has an amino acid sequence homology of 96% with mouse C4ST. When the cDNA was introduced into a eukaryotic expression vector and transfecte d in COS-7 cells, the sulfotransferase activity that transfers sulfate to b oth chondroitin and desulfated dermatan sulfate was overexpressed, Northern blot analysis indicated that human C4ST mRNAs (6.0 and 1.9 kb) are express ed ubiquitously in various adult human tissues. Dot blot analysis has shown that human C4ST is strongly expressed in colorectal adenocarcinoma and per ipheral blood leukocytes, whereas strong expression of human chondroitin B- sulfotransferase (C6ST) is observed in aorta and testis, These observations suggest that the expression of C4ST and C6ST may be controlled differently in human tissues. The C4ST gene was localized to chromosome 12q23.2-q23.3 by fluorescence in situ hybridization.