The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function.
We have constructed novel chimeric receptors, GAL-ER and GAL-GR, consisting of the DNA-binding domain of the yeast transcription factor GAL4 joined to the C-terminal region containing the hormone-binding domain of either the human estrogen (hER) or human glucocorticoid (hGR) receptor. Stimulation of transcription by GAL-ER and GAL-GR from GAL4-responsive reporter genes was hormone dependent, and the activation function has been localized to the hER or hGR region. Both chimeric receptors recognized GAL4-responsive elements only in the presence of hormone or anti-hormone, yet solely the hormone was capable of stimulating transcription. These and additional results suggest that the hormone plays at least a dual role. First, the hormone, or anti-hormone, is responsible for receptor "transformation" allowing the recognition of responsive DNA elements. Second, the hormone, but not the anti-hormone, can induce a transcription activation function present in the region that contains the hormone-binding domain.
Webster
N J
NJ
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Strasbourg, France.
Green
S
S
Jin
J R
JR
Chambon
P
P
D004247:DNA / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism; D006367:HeLa Cells; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D015735:Mifepristone; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004963:Estrenes; D004965:Estrogen Antagonists; D004967:Estrogens; D005938:Glucocorticoids; D006728:Hormones; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D013629:Tamoxifen; C016601:afimoxifene; D015735:Mifepristone; D004958:Estradiol; C051781:ICI 164384; D004247:DNA