FIG. 10.

Two possible mechanisms for the recruitment of Oct-1/2 by GR to octamer motifs adjacent to GREs. (A) Upon treatment with steroid, liganded GR is transported into the nucleus, where it can form a complex with Oct-1/2 through an interface that involves the zinc fingers of GR and the POU domain of Oct-1/2 (step i). Mutations L501P and C500Y in the GR DBD specifically abrogate octamer factor binding. Although the binding to Oct-1/2 requires determinants in the GR DBD, GR complexed with Oct-1/2 retains the ability to recognize and bind to a GRE (step ii). Binding of GR to a GRE is preferred to, and destabilizes, binding to Oct-1/2. During the course of GR DNA binding, the interaction between GR and Oct-1/2 is weakened in a manner that leads to the release of the octamer factor from GR in vitro. In the absence of nearby octamer motifs, the octamer factor is not retained. However, in the presence of an adjacent octamer motif, the release of Oct-1/2 directly promotes octamer motif binding (step iii). (B) The second mechanism is similar to that shown in panel A, except that the associated GR and octamer factors bind coordinately to transcriptional regulatory regions containing GREs and octamer motifs linked in cis. Coordinate binding may potentially occur in preference to binding by the individual factors to regulatory regions with binding sites for only GR or Oct-1/2.