Specific binding of progesterone receptor to progesterone-responsive elements does not require prior dimerization.
Steroid-hormone receptors undergo, prior to binding to DNA, a hormone-dependent dimerization. It is generally accepted that this dimerization is indispensable for the high-affinity binding of hormone receptor to hormone-responsive elements. Using a progesterone-receptor mutant with the complete steroid-binding domain deleted (positions 663-930), with or without the epitope required for binding the monoclonal antibody Let 126, we have shown that this receptor species was unable to undergo dimerization in solution. However, this mutant retained a high affinity (60-70% of the affinity of the wild-type receptor) for the progesterone-responsive elements of the mouse-mammary-tumor-virus long-terminal-repeat promoter and for a consensus palindromic progesterone-responsive element, as measured by both DNase-I protection experiments and gel-shift experiments. This mutant also increased gene transcription. Thus, at least in the case of the progesterone receptor, prior dimerization is dispensable for receptor binding to regulatory DNA elements and for subsequent transcription activation.
Cohen-Solal
K
K
Unité de Recherche Hormones et Reproduction, Faculté de Médecine, Paris-Sud, Le Kremlin-Bicêtre, France.
Bailly
A
A
Rauch
C
C
Quesne
M
M
Milgrom
E
E
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes; D008324:Mammary Tumor Virus, Mouse / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D011108:Polymers; D011980:Receptors, Progesterone / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics
D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D000939:Epitopes; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D011980:Receptors, Progesterone; D003850:Deoxyribonuclease I