Cloning, expression and regulation of the human S14 gene

The rat S14 gene has been a useful model to study carbohydrate and triiodothyronine (T3) regulation of hepatic gene expression. To gain insight into the regulation and function of the S14 gene, we isolated the human S14 gene and studied its sequence, tissue specific expression, and transcriptional regulation by glucose and T3. The deduced amino acid sequence of the human S14 protein is 78% identical to that of the rat. Northern blot analysis showed that the S14-mRNA is a single species in human liver and is not present in human brain or HepG2 cells. Transfection studies in primary hepatocytes revealed that transcription of the human S14 gene is regulated by glucose and T3 in a similar manner to that of the rat gene. However, in HepG2 cells, T3 and glucose did not affect the transcription of the human S14 gene. These observations suggest that the S14 gene is highly conserved in mammals and is similarly regulated by carbohydrate and T3 in vivo. More importantly, the function of the human S14 gene may be critical in lipid metabolism in human liver as the rat S14 gene is in rodents.