title: Role of chromatin structure in transcriptional regulation of MMTV LTR hormone-dependent promoter.
abstract: Studies of chromatin structure were performed in mouse fibroblast cell lines containing Bovine Papilloma Virus (BPV) based artificial minichromosomes containing Mouse Mammary Tumor Virus (MMTV) Long Terminal Repeat (LTR), a retroviral promoter regulated by glucocorticoids, driving the transcription of v-Ha-ras. These minichromosomes fractionate with the "active chromatin", indicating an association of the minichromosomes with components of the "nuclear matrix". Two regions of the minichromosomes upstream and downstream of v-Ha-ras are involved in this interaction. MMTV LTR promoter is associated with nucleosomes precisely positioned on the DNA sequences. Hormonal activation is accompanied by a structural change of the nucleosome associated with the hormone response elements (HREs). This structural change can be visualized by the appearance of a hormono-dependent DNaseI hypersensitive site. Anti-hormones, even when able to promote a strong binding of the receptor to the nucleus, are unable to induce the chromatin structural change. The strong association of the hormone-receptor complex with the nucleus is necessary to induce the DNaseI hypersensitive site and to maintain the transcription, but is not necessary for DNaseI hypersensitivity maintenance. This suggests a double role for the hormone-receptor complex: 1) induction of a chromatin rearrangement and 2) transcriptional transactivation.
authors.affiliation: Unité de Recherches sur les communications hormonales, INSERM U-33, Hôpital du Kremlin Bicêtre, France.
authors.forename: H
authors.initials: H
authors.lastname: Richard-Foy
authors.forename: J
authors.initials: J
authors.lastname: Adom
authors.forename: K
authors.initials: K
authors.lastname: Carr
authors.forename: F
authors.initials: F
authors.lastname: Gouilleux
authors.forename: V
authors.initials: V
authors.lastname: Marsaud
authors.forename: G
authors.initials: G
authors.lastname: Redeuilh
authors.forename: M
authors.initials: M
authors.lastname: Sabbah
authors.forename: B
authors.initials: B
authors.lastname: Sola
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure*; D004274:DNA, Recombinant / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D005813:Genes, Synthetic; D005814:Genes, Viral; D005822:Genetic Vectors; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008968:Molecular Conformation; D009707:Nucleosomes / Q000648:ultrastructure; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D002843:Chromatin; D004274:DNA, Recombinant; D009707:Nucleosomes; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; C028697:dexamethasone receptor; D003907:Dexamethasone; D015689:Oncogene Protein p21(ras)