THE CARBOXY-TERMINAL TRANSACTIVATION DOMAIN OF OCT-4 ACQUIRES CELL-SPECIFICITY THROUGH THE POU DOMAIN

The POU transcription factor Oct-4 is expressed in totipotent and plur ipotent cells of the early mouse embryo and the germ cell lineage, Tra nsactivation capacities of regions flanking the DNA binding domain of Oct-4 were analyzed in undifferentiated and differentiated cell lines, The amino- and carboxy-terminal regions (N domain and C domain) fused to the Gall DNA binding domain both functioned as transactivation dom ains in all cell lines tested. However, the C domain failed to activat e transcription in some cell lines in the context of the native protei n. The underlying regulator, mechanism appears to involve the POU doma in of Oct-4 and can discriminate between different POU domains, since constructs in,which the C domain was instead fused to the POU domain o f Pit-1 were again equally active in all cell lines, These results ind icate that the C domain is subject to cell-type-specific regulation me diated by the Oct-4 POU domain. Phosphopeptide analysis revealed that the cell-type-specific difference of C-domain activity correlates with a difference in Oct-4 phosphorylation status, Since Oct-4 is expresse d in a variety of distinct cell types during murine embryogenesis, the se results suggest an additional regulatory mechanism for determining Oct-4 function in rapidly changing cell types during development.