Interaction of steroid hormone receptors with transcription factors involves chromatin remodelling.

ABSTRACT

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 transcription factors, as well as with sequence-specific transcription factors. Moreover co-activators or transcription intermediary factors, have been identified which could mediate some of the transcriptional effects of the hormone-receptor complex. However, in addition to this interaction of receptors with proteins directly involved in transcription, a participation of chromatin structure in gene regulation by steroid hormones is becoming increasingly evident. In the case of the MMTV promoter, the nucleosomal organization seems to be responsible for transcriptional repression prior to hormonal stimulation. This effect is due to 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 sequence specific transcription factors to assemble on the promoter. Since a complete occupancy of binding sites does not take place when the promoter is present as naked DNA, the nucleosomal organization appears to be required for the proper synergism between transcription factors following hormonal induction. According to this model, the positioning of a nucleosome sets the stage for constitutive repression and hormone induction of the MMTV promoter.