AP-1 AND OCT-1 TRANSCRIPTION FACTORS DOWN-REGULATE THE EXPRESSION OF THE HUMAN PIT1 GHF1 GENE/

The pituitary-specific transcription factor Pit-1/GHF-1 is a member of the POU domain family of regulatory proteins, It is involved in the c ommitment and expansion of the somatotropic cell lineage and activates the transcription of a set of anterior pituitary genes. We have clone d the human PIT1/GHF1 gene and characterized the regulatory mechanisms controlling its promoter activation and regulation. A minimal promote r region (-102 to +15) contains the cis-acting elements that confer to the human PIT1/GHF1 gene a high basal transcriptional activity, the t issue-specific expression, and the autoregulation by Pit-1/GHF-1 prote in. The upstream promoter region contains a multiplicity of Pit-1/GHF- 1 binding sites that do not show any synergistic interaction with the minimal promoter, The transcriptional activity is negatively regulated by Oct-1 and mediated by an octamer-binding site (OTF). In addition, we have also identified a 12-O-tetradecanoylphorbol-13-acetate-respons ive element, which overlaps with a Pit-1/GHF-1 binding site. A mutuall y exclusive binding of the activator protein-1 (AP-1) and Pit-1/GHF-1 has been observed on this composite site, and AP-1 was shown to down-r egulate PIT1/GHF1 transcription.