INTERACTION OF STEROID-HORMONE RECEPTORS WITH TRANSCRIPTION FACTORS INVOLVES CHROMATIN REMODELING

The mechanism by which steroid hormones modulate promoter utilization is not clear. Evidence from transfection studies and cell-free assays points to an interaction of the hormone receptors with general transcr iption factors, as well as with sequence-specific transcription factor s. Moreover co-activators or transcription intermediary factors, have been identified which could mediate some of the transcriptional effect s of the hormone-receptor complex. However, in addition to this intera ction of receptors with proteins directly involved in transcription, a participation of chromatin structure in gene regulation by steroid ho rmones is becoming increasingly evident. In the case of the MMTV promo ter, the nucleosomal organization seems to be responsible for transcri ptional repression prior to hormonal stimulation. This effect is due t o occlusion by a nucleosome positioned on the MMTV promoter sequences in such a way that essential transcription factors cannot access their recognition sites. Following hormone induction, a remodelling of the nucleosome structure takes place which enables a whole complement of s equence specific transcription factors to assemble on the promoter. Si nce a complete occupancy of binding sites does not take place when the promoter is present as naked DNA, the nucleosomal organization appear s to be required for the proper synergism between transcription factor s following hormonal induction. According to this model, the positioni ng of a nucleosome sets the stage for constitutive repression and horm one induction of the MMTV promoter.