Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the mouse mammary tumor viruspromoter

Transcriptional synergism between glucocorticoid receptor (GR) and octamer transcription factors 1 and 2 (Oct-1 and Oct-2) in the induction of mouse m ammary tumor virus (MMTV) transcription has been proposed to be mediated th rough directed recruitment of the octamer factors to their binding sites in the viral long terminal repeat. This recruitment correlates with direct bi nding between the GR DNA binding domain and the POU domain of the octamer f actors. In present study, in vitro experiments identified several nuclear h ormone receptors to have the potential to bind to the POU domains of Oct-1 and Oct-2 through their DNA binding domains, suggesting that POU domain bin ding may be a property shared by many nuclear hormone receptors, However, p hysiologically relevant binding to the POU domain appeared to be a property restricted to only a few nuclear receptors as only GR, progesterone recept or (PR), and androgen receptor (AR), were found to imteract physically and functionally with Oct-1 and Oct-2 in transfected cells. Thus GR, PR, and AR efficiently promoted the recruitment of Oct-2 to adjacent octamer motifs i n the cell, whereas mineralocorticoid receptor (MR), estrogen receptor alph a, and retinoid X receptor failed to facilitate octamer factor DNA binding. For MMTV, although GR and MR both induced transcription efficiently, mutat ion of the promoter proximal octamer motifs strongly decreased OR-induced t ranscription without affecting the total level of reporter gene activity in response to MR, These results suggest that the configuration of the hormon e response element within the MMTV long terminal repeat may promote a depen dence for the glucocorticoid response upon the recruitment of octamer trans cription factors to their response elements within the viral promoter.