title: Specific deactivation of the mouse mammary tumor virus long terminal repeat promoter upon continuous hormone treatment.
abstract: We have studied the transcriptional behavior of the mouse mammary tumor virus long repeat (MMTV-LTR) promoter during a prolonged exposure to glucocorticoids. When integrated into XC-derived cells, MMTV-LTR expression reached its maximum during the first day of dexamethasone treatment, but longer exposure to the hormone resulted in the deactivation of the promoter. In contrast, glucocorticoid-responsive resident genes or MMTV-based transiently transfected plasmids maintained or even increased their mRNA levels during the same period of hormone treatment. An integrated chimeric construct containing the hormone-responsive elements from MMTV-LTR but in different sequence context became also deactivated after a prolonged hormone treatment but with a deactivation kinetics significantly slower than constructs containing the entire, chromatin-positioning MMTV-LTR sequence. The decrease on MMTV-LTR-driven transcription was concomitant with a parallel closure of the MMTV-LTR chromatin and with a decrease in glucocorticoid receptor (GR) concentration in the cell. We concluded that the chromatin-organized MMTV-LTR promoter is particularly sensitive to any decrease on GR levels. We propose that chromatin structure may contribute decisively to the differential expression of MMTV-LTR by two mechanisms: limiting MMTV-LTR accessibility to activating transcription factors and accelerating its shutting down upon a decrease on GR levels.
authors.affiliation: Departament de Biologia Molecular i Cel.lular, Centre d'Investigació i Desenvolupament, Consejo Superior de Investigaciones Científicas, C/Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Boronat
authors.forename: H
authors.initials: H
authors.lastname: Richard-Foy
authors.forename: B
authors.initials: B
authors.lastname: Piña
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D006224:Cricetinae; D003850:Deoxyribonuclease I / Q000378:metabolism; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008324:Mammary Tumor Virus, Mouse / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects / Q000235:genetics*; D014162:Transfection
chemical_list: D002843:Chromatin; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003850:Deoxyribonuclease I