Pregnancy-specific glycoprotein 5 human gene (PSG5) belongs to a family of highly similar and active genes. High levels of PSG biosynthesis are restricted to the placental syncytiotrophoblast and are essential for the maintenance of normal gestation. PSG5 promoter contains a GC-like box recognized by the ubiquitous Sp1 transcription factor. Now, we have characterized the regulatory region that represses PSG5 expression. EMSA and UV-crosslinking assays revealed that the -543/-517 cis element, included in a negative regulatory region, is specifically recognized by a protein of 115 KDa present in PSG-non-expressing cell lines and absent in human term placenta extracts. Dissection of the negative regulatory region in PSG5-CAT constructs showed that at least two elements, including -543/-517, mediate repressed transcriptional activity in transient-expression assays. These negative acting modules are specific of PSG5 promoter since no repression was observed on heterologous promoters.
In addition, we examined the role of transcriptional activators of placenta-specific genes in PSG5 regulation. SNURF co-activator was able to enhance transcription even in the presence of the repressive region, while GCMa transcription factor did it sinergically with Sp1 only when this module was absent.
We propose that placenta specific expression of PSG5 gene is mainly achieved through an impairment of the repressor functions that allows high levels of expression through the action of the identified transcriptional activators.
