Transcriptional control by steroid hormones: the role of chromatin.

The mouse mammary tumour virus (MMTV) promoter contains a complex hormone-responsive unit composed of four hormone-responsive elements, a nuclear factor I (NFI) binding site and two octamer motifs. All these sites are required for optimal hormonal induction. Although synergism has been found between hormone receptors and octamer transcription factor 1 (Oct-1/OTF-1), we were unable to detect a positive interaction between receptors and NFI in vitro. In chromatin, the MMTV hormone-responsive unit is contained in a phased nucleosome. The precise positioning of the DNA double helix on the surface of the histone octamer precludes binding of NFI and Oct-1/OTF-1 to their cognate sequences, while still allowing recognition of two hormone-responsive elements by the hormone receptors. Hormone treatment leads to a characteristic change in chromatin structure that makes the centre of the nucleosome more accessible to digestion by DNase I and facilitates binding of receptors, NFI and Oct-1/OTF-1 to the nucleosomally organized promoter. The MMTV promoter functions in yeast in a hormone receptor-dependent and NFI-dependent fashion. Depletion of nucleosomes activates hormone-independent transcription from the MMTV promoter. These results imply that nucleosome positioning not only represses hormone-independent transcription, but also enables binding of a full complement of transcription factors to the hormone-responsive unit after hormone induction.