Repression of Oct-4 during embryonic cell differentiation correlates with the appearance of TRIF, a transiently induced DNA-binding factor

The Oct-4 gene encodes a transcription factor that is essential for maintai ning the mouse germline. It is expressed during the earliest stages of embr yogenesis, is downregulated during gastrulation, and is thereafter constrai ned to the germ cell lineage. Retinoic acid induced differentiation of embr yonal carcinoma cells is also accompanied by a decrease in Oct-4 expression . We have previously shown that downregulation of Oct-4 expression is media ted by a hormone regulatory element (HRE). This element is located within t he basal promoter and overlaps with a GC box that is crucial for Oct-4 prom oter activity. The HRE is composed of three direct repeats with 1 and 0 spa cing. In this study, we demonstrate that the doublet of direct repeats with 0 spacing (DR0) is bound by two novel factors. The initial repression of O ct-4 by retinoic acid coincides with the disappearance of the first factor (named UCF for undifferentiated cellular factor) and the appearance of a tr ansiently induced factor (TRIF) which forms a larger complex with DR0 in el ectrophoretic mobility shift assays. These observations support the hypothe sis that downregulation of the Oct-4 gene during early mouse embryogenesis involves the repression of its promoter by TRIF.