Sequences within the 5'-flanking region of the S14 gene confer responsiveness to glucose in primary hepatocytes.

The DNA sequences involved in control of S14 gene expression in response to carbohydrate have been studied. The levels of S14 mRNA in primary hepatocytes increase when glucose in the media is elevated from 5.5 to 27.7 mM in the presence of insulin. Following lipofection of primary hepatocytes, plasmids containing S14 genomic sequences from -4316 to +19 relative to the start of transcription were sufficient to confer glucose regulation to the linked marker gene, chloramphenicol acetyltransferase. Deletions of the S14 sequences between -4316 and -1601 led to a significant reduction in glucose-stimulated activity with each successive deletion, suggesting the presence of multiple regulatory elements. The response of the transfected construct containing 4316 base pairs of S14 5'-flanking region mimicked changes in the endogenous S14 mRNA levels in all hormonal and nutritional conditions tested, supporting the physiological significance of the response.