AP-1 and Oct-1 Transcription Factors Down-regulate the Expression of the Human PIT1/GHF1 Gene

Abstract

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 commitment and expansion of the somatotropic cell lineage and activates the transcription of a set of anterior pituitary genes. We have cloned the human PIT1/GHF1 gene and characterized the regulatory mechanisms controlling its promoter activation and regulation. A minimal promoter region (؊102 to ؉15) contains the cis-acting elements that confer to the human PIT1/GHF1 gene a high basal transcriptional activity, the tissue-specific expression, and the autoregulation by Pit-1/GHF-1 protein. 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-responsive element, which overlaps with a Pit-1/ GHF-1 binding site. A mutually 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-regulate PIT1/GHF1 transcription.

Repression of Virus-Induced Interferon A Promoters by Homeodomain Transcription Factor Ptx1

“…With regard to previously reported results concerning the overexpression of Ptx1 which led to activation of the POMC and other pituitary genes (13,37), the effects of Ptx1 vary with promoter context, and this is the first demonstration that Ptx1 (6). The present study shows that the HD transcription factor Ptx1 can modulate POMC or other pituitary genes and IFN-A gene expression differently.…”

Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy

“…The series of events we describe in R7E mice, leading to c-Jun-mediated Nrl repression, appear to be very similar. Furthermore, c-Jun/AP-1 has been shown to repress expression of tissue-specific genes, including osteocalcin, a bone-specific marker and the pituitary-specific transcription factor (Pit-1/GHF-1) (Owen et al, 1990;Delhase et al, 1996). Interestingly, in both cases, the repression mechanism involves a mutually exclusive occupancy of AP-1 and tissue-specific transcription factors.…”

Protein Kinase A-Dependent Derepression of the Human Prodynorphin Gene via Differential Binding to an Intragenic Silencer Element

“…The IGF-I-mediated increase in elastin transcription occurs via a mechanism of derepression that involves activation of a retinoblastoma control element by nuclear complexes which contain the Rb protein following the abrogation of Sp3 repressor binding (9). In the case of the Pit1/GHF1 gene, the release of AP-1 complexes allows the Pit1/GHF1 protein to act at an enhancer site close to the AP-1 site, thus causing upregulation of the gene (10). Furthermore, a mechanism of derepression mediated by distal regulatory elements has been proposed in the rat prodynorphin gene (8).…”