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

Abstract

The Oct-4 gene encodes a transcription factor that is essential for maintaining the mouse germline. It is expressed during the earliest stages of embryogenesis, is downregulated during gastrulation, and is thereafter constrained to the germ cell lineage. Retinoic acid induced differentiation of embryonal carcinoma cells is also accompanied by a decrease in Oct-4 expression. We have previously shown that downregulation of Oct-4 expression is mediated by a hormone regulatory element (HRE). This element is located within the basal promoter and overlaps with a GC box that is crucial for Oct-4 promoter activity. The HRE is composed of three direct repeats with 1 and 0 spacing. 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 Oct-4 by retinoic acid coincides with the disappearance of the first factor (named UCF for undifferentiated cellular factor) and the appearance of a transiently induced factor (TRIF) which forms a larger complex with DR0 in electrophoretic mobility shift assays. These observations support the hypothesis that downregulation of the Oct-4 gene during early mouse embryogenesis involves the repression of its promoter by TRIF.