Six human beta-galactoside alpha2,3-sialyltransferase genes, which are hST3Gal I-VI, have been cloned. Multiple genes encode enzymes with closely related catalytic specificities but different patterns of tissue expression. The multiple genes correspond to the control of various tissue specific regulators. Several studies have examined the transcriptional regulation of some human beta-galactoside alpha2,3-sialyltransferases genes. Multiple mRNA forms differing only in the 5'-untranslated regions have been identified in hST3Gal II, hST3Gal III, hST3Gal IV, hST3Gal V, and hST3Gal VI. These transcripts are produced by a combination of alternative splicing and promoter utilization, suggesting the transcriptional regulation of this gene depends on the use of alternative promoters, further suggesting that tissue-specific transcriptional regulation of these genes depends on the use of multiple genes and multiple promoters. The multiple regulatory pathways of these ubiquitous sialyltransferases may be differentially modulated in various cell types.