Transcriptional regulation of the cellular retinoic acid binding protein Igene in F9 teratocarcinoma cells

Retinoic acid (RA) induces the differentiation of many murine teratocarcino ma cell lines such as F9 and P19. In F9 cells, the level of the cellular re tinoic acid binding protein I (CRABP I) mRNA is greatly reduced after expos ure of the cultured cells to exogenous RA. In P19 cells, the level of CRABP I mRNA is greatly increased after RA exposure. We have identified a 176-bp region in the murine CRABP I promoter, between -2.9 and -2.7 kb 5' of the start site of transcription, which acts as an enhancer in undifferentiated F9 stem cells and through which RA effects inhibition of CRABP I transcript ion. Within this region are two footprinted sites at -2763 and -2834, This 176-bp regulatory region does not function to enhance CRABP I transcription in P19 stem cells. Several DNA sequences within these two footprinted regi ons bind proteins from F9 nuclear extracts but not from pig nuclear extract s (e.g., FP1B, FP1A, and FP2B), as assessed by gel shift Essays. This 176-b p CRABP I genomic region has not been sequenced previously and functionally analyzed in cultured cells because it was not present in the murine CRABP I clones used for the promoter analyses reported earlier by another laborat ory. The function of this enhancer may be to reduce the expression of the C RABP I gene in specific embryonic cell types in order to regulate the amoun t of RA to which the cells are exposed.