GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes

摘要

The glucocorticoid receptor regulates liver-specific expression of the tryptophan oxygenase gene through glucocorticoid responsive elements located ?0.45 and ?1.2 kb from the transcription start site. However, the hormone-mediated induction is restricted to adult hepatocytes, and fetal hepatocytes are unable to express the gene even in the presence of the receptor and glucocorticoid hormone. The difference in sensitivity to the hormone between adult and fetal hepatocytes has not been well understood. In this study, we analyzed the structure of the tryptophan oxygenase gene’s promoter. The promoter has two TATA boxes, and transcription starts from the downstream TATA box. We found that a transcription factor GATA4 bound to the downstream TATA box and may inhibit the binding of TATA-binding protein, resulting in transcriptional repression even in the presence of glucocorticoid in fetal hepatocytes.