AN OCTAMER MOTIF CONTRIBUTES TO THE EXPRESSION OF THE RETINOIC ACID-REGULATED ZINC FINGER GENE REX-1 (ZFP-42) IN F9 TERATOCARCINOMA CELLS

The message for the zinc finger gene Rex-1 (Zfp-42) is expressed in un differentiated murine F9 teratocarcinoma cells and embryonic stem cell s. Expression of Rex-1 is reduced at the transcriptional level when F9 cells are induced by the addition of retinoic acid (RA) to differenti ate. We have isolated genomic DNA for the Rex-1 gene (Zfp-42), charact erized the gene's structure, and mapped the gene to mouse chromosome 8 . Promoter elements contributing to the regulation of the Rex-1 promot er in F9 cells have been identified. A region required for Rex-1 promo ter activity in F9 stem cells contains an octamer motif (ATTTGCAT) whi ch is a binding site for octamer transcription factor members of the P OU domain family of DNA-binding proteins. Rex-1 reporter plasmids incl uding this octamer site also exhibited reduced expression in F9 cells treated with RA. Thus, the octamer motif is a regulatory element requi red for the activity of the Rex-1 promoter in F9 stem cells, and this motif contributes to the negative regulation by RA of the transcriptio n of the Rex-1 gene. As an initial confirmation of the in vivo relevan ce of the isolated fragment, a larger Rex-1 promoter fragment, also co ntaining the octamer site, was able to promote expression of the bacte rial lacZ gene in mouse embryos at the morula stage.