Two-step synergism between the progesterone receptor and the DNA-binding domain of nuclear factor 1 on MMTV minichromosomes

In contrast to its behavior as naked DNA, the MMTV promoter assembled in mi nichromosomes can be activated synergistically by the progesterone receptor and NF1 in a process involving ATP-dependent chromatin remodeling. The DNA -binding domain of NF1 is required and sufficient for stable occupancy of a ll receptor-binding sites and for functional synergism. Activation of purif ied minichromosomes is observed in the absence of SWI/SNF and can be enhanc ed by recombinant ISWI. Receptor binding to minichromosomes recruits ISWI a nd NURF38, but not brahma. We propose a two-step synergism in which the rec eptor triggers a chromatin remodeling event that facilitates access of NF1, which in turn stabilizes an open nucleosomal conformation required for effi cient binding of further receptor molecules and full transactivation.