FIGURE 5.

Model for the initial steps of MMTV promoter activation. Before hormone addition the MMTV promoter is silent and associated with a repressive complex that includes HP1g (step 1). After hormone addition the activated complex of pPR-pErk-pMsk, and likely PCAF and BAF, is recruited to the MMTV promoter (step 2). For simplicity PR is shown as a monomer, although the active form is a homodimer. This complex phosphoacetylates H3 leading to H3S10phK14ac, a modification that displaces the repressive complex (step 3) and anchors the BAF complex leading to ATP-dependent H2A/H2B displacement (step 4). The nucleosome opening facilitates NF1 binding (step 5). In the absence of NF1, the open conformation reverts to the repressed state (step 6), whereas NF1 binding to its cognate site maintains the open H3/H4 tetramer conformation (step 7) and facilitates binding of further PR and associated factors to the previously inaccessible HREs (step 8), thus promoting the recruitment of coactivators and the general transcriptional machinery (step 9). How this fully loaded promoter on a H3/H4 tetramer is further converted into a preinitiation complex (step 10) is unknown.