Antiprogestins mediate differential effects on glucocorticoid receptor remodeling of chromatin structure.
We examined the mechanism(s) by which the progesterone receptor (PR) is able to inhibit glucocorticoid receptor (GR) activation from the mouse mammary tumor virus (MMTV) promoter in vivo. Using specific hormone antagonists, we demonstrate that the PR complexed with an type II antiprogestin blocks glucocorticoid-induced activation of the MMTV promoter. However, when complexed with a type I antiprogestin the PR is unable to block glucocorticoid-induced activation. PR repression of GR activity results from the inhibition of the ability of the GR to remodel chromatin such that the antiprogestin-occupied/PR prevents the glucocorticoid induced assembly of a preinitiation complex at MMTV promoter. These experiments suggest that the specific chromatin organization of the MMTV promoter provides a mechanism for regulating cross-talk between the GR and PR in vivo.
Fryer
C J
CJ
Department of Ob/Gyn, Biochemistry and Oncology, The University of Western Ontario, London Regional Cancer Centre, London, Ontario N6A 4L6, Canada.
Nordeen
S K
SK
Archer
T K
TK
D002843:Chromatin / Q000737:chemistry*; D003907:Dexamethasone / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D008958:Models, Molecular; D011374:Progesterone / Q000037:antagonists & inhibitors*; D011487:Protein Conformation; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D002843:Chromatin; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D011374:Progesterone; D003907:Dexamethasone