[en] Steroid induction of responsive genes functions through the synergistic activity of steroid receptor-binding sequences with adjacent transcription factor-binding sites. To analyze the mechanism of synergy we tested different human glucocorticoid receptor mutants for synergistic function with another transcription factor in comparison with intrinsic trans-activation obtained with a single receptor binding site (glucocorticoid response element). Multiple domains were found to be involved in synergistic activity of the glucocorticoid receptor with the CACCC box factor. Deletions within the N-terminal receptor half affected simultaneously intrinsic trans-activation and synergism. However, deletion of the hormone-binding domain mainly impaired synergism rather than intrinsic trans-activation, clearly showing that this domain synergizes by a mechanism independent of intrinsic activation. A chimeric protein where the DNA-binding domain of the glucocorticoid receptor was replaced by that of the yeast GAL4 protein also showed functional synergism. These data suggest that some of the receptor domains outside the DNA-binding domain synergize by their intrinsic trans-activating property, but the hormone-binding domain contributes to synergism by a different mechanism.
Disciplines :
Genetics & genetic processes
Author, co-author :
Muller, Marc ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Baniahmad, C.
Kaltschmidt, C.
Renkawitz, R.
Language :
English
Title :
Multiple domains of the glucocorticoid receptor involved in synergism with the CACCC box factor(s).
Publication date :
1991
Journal title :
Molecular Endocrinology
ISSN :
0888-8809
eISSN :
1944-9917
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
Ankenbauer W, Strähle U, Schütz G 1988 Synergisticaction of glucocorticoid and estradiol responsive elements. Proc Natl Acad Sei USA 85:7526-7530
Baniahmad A, Muller M, Steiner Ch, Renkawitz R 1987 Activity of two different silencer elements of the chickenlysozyme gene can be compensated by enhancer elements. EMBO J 6:2297-2303
Beato M 1989 Gene regulation by steroid hormones. Cell 56:335-344
Brüggemeier U, Kalff M, Franke S, Scheidereit K, Beato M 1991 Ubiquitous transcription factor OTF-1 mediatesinduction of the MMTV promoter through synergistic interaction with hormone receptors. Cell 64:565-572
Carey M, Kakidani H, Leatherwood J, Mostashari F, Ptashne M 1989 An amino-terminal fragment of GAL4binds DNA as a dimer. J Mol Biol 209:423-432
Cato ACB, Miksicek R, Schütz G, Arnemann J, Beato M 1986 The hormone regulatory element of mouse mammary tumor virus mediates progesterone inducibility.EMBO J 5:2237-2240
Cato ACB, Heitlinger E, Ponta H, Klein-Hitpass L, Ryffel GU, Bailly A, Rauch C, Milgrom E 1988 Estrogen andprogesterone receptor-binding sites on the chicken vitellogenin II gene: synergism of steroid hormone action. MolCell Biol 8:5323-5330
Dynan WS 1989 Modularity in promoters and enhancers.Cell 58:1-4
Giguere V, Hollenberg SM, Rosenfeld MG, Evans RM 1986 Functional domains of the human glucocorticoidreceptor. Cell 46:645-652
Giniger E, Ptashne M 1988 Cooperative DNA binding ofthe yeast transcriptional activator GAL4. Proc Natl AcadSci USA 85:382-386
Gorman CM, Moffat LF, Howard BH 1982 Recombinantgenomes which express chloramphenicol acetyltransfer-ase in mammalian cells. Mol Cell Biol 2:1044-1051
Hollenberg SM, Giguere V, Segui P, Evans RM 1987 Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor. Cell49:39-46
Hollenberg SM, Evans RM 1988 Multiple and cooperativefrans-activation domains of the human glucocorticoid receptor. Cell 55:899-906
Keegan L, Gill G, Ptashne M 1986 Separation of DNAbinding from the trans-activation function of a eucaryoticregulatory protein. Science 231:699-704
Klein-Hitpaβ L, Kaling M, Ryffel GU 1988 Synergism ofclosely adjacent estrogen-responsive elements increasestheir regulatory potential. J Mol Biol 201:537-544
Lewin B 1990 Commitment and activation at Pol II ofprotein-protein interactions. Cell 61:1161-1164
Ma J, Ptashne M 1987 Deletion analysis of GAL4 definestwo transcriptional activating fragments. Cell 48:847-853
Ma J, Ptashne M 1987 A new class of yeast transcriptionalactivators. Cell 51:113-119
Martinez E, Wahli W 1989 Cooperative binding of estrogen receptor to imperfect estrogen-responsive DNA elements correlates with their synergistic hormone-dependent enhancer activity. EMBO J 8:3781-3791
Muller M, Baniahmad C, Kaltschmidt C, Schüle R, Ren-kawitz R 1990 Cooperative frans-activation of steroidreceptors. In: Parker M (ed) Nuclear Hormone Receptors.Academic Press, London, pp 155-174
Nalimov VV 1963 The Application of Mathematical Statistics to Chemical Analysis. Pergamon Press, Oxford
Ponglikitmongkol M, White JH, Chambon P 1990 Synergistic activation of transcription by the human estrogenbound to tandem responsive elements. EMBO J 9:2221-2231
Ptashne M 1988 How eukaryotic transcriptional activatorswork. Nature 335:683-689
Schüle R, Muller M, Kaltschmidt C, Renkawitz R 1988Many transcription factors interact synergistically withsteroid receptors. Science 242:1418-1420
Schüle R, Muller M, Otsuka-Murakami H, Renkawitz R1988 Cooperativity of the glucocorticoid receptor and theCACCC-box binding factor. Nature 332:87-90
Strähle U, Schmid W, Schütz G 1988 Synergistic actionof the glucocorticoid receptor with transcription factors. EMBO J 7:3389-3395
Tasset D, Tora L, Fromental C, Scheer E, Chambon P 1990 Distinct classes of transcriptional activating domainsfunction by different mechanisms. Cell 62:1177-1187
Tora L, White J, Brou C, Tasset D, Webster N, Scheer E, Chambon P 1989 The human estrogen receptor has twoindependent nonacidic transcriptional activation functions.Cell 59:477-487
Webster NJG, Green S, Jin JR, Chambon P 1988 Thehormone binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function. Cell 54:199-207
