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.
Truss
M
M
Institut für Molekularbiologie und Tumorforschung, Philipps Universität, Marburg, Germany.
Candau
R
R
Chávez
S
S
Beato
M
M
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D013256:Steroids / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D013256:Steroids; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D004247:DNA