Estrogen-inducible derivatives of hepatocyte nuclear factor-4, hepatocyte nuclear factor-3 and liver factor B1 are differently affected by pure and partial antiestrogens.
The tissue-specific transcription factors of the hepatocyte nuclear factor-4 (HNF4), hepatocyte nuclear factor-3 (HNF3), and liver factor B1 (LFB1) families are thought to play a role in the development of internal organs and in the tissue-specific expression of many distinct genes. We have now constructed derivatives of these proteins by introducing the hormone-binding domain of the estrogen receptor and show that in transient transfections these chimeric proteins act as estrogen-inducible transcription factors with the DNA sequence specificity of the original factors. These chimeric transcription factors are differently affected by the partial estrogen antagonist 4-hydroxytamoxifen and the pure antiestrogen N-n-butyl-11-(3,17-dihydroxy-estra-1,3,5(10)-trien- 7 alpha-yl)N-methyl-undecamide (ICI 164384); 4-hydroxytamoxifen activates, at least partially, all the chimeric factors and the estrogen receptor, while ICI 164384 surprisingly activates the transcription factors derived from HNF3 and LFB1 and inhibits only the estrogen receptor and the HNF4 derivative. Together with the DNA-sequence-binding specificity, the different response to estrogen and anti-estrogens makes our estrogen receptor fusion proteins useful tools for the investigation of the roles of HNF4, HNF3 and LFB1 in gene expression, differentiation and developmental processes.
Drewes
T
T
Institut für Zellbiologie, Universitätsklinikum Essen, Germany.
Clairmont
A
A
Klein-Hitpass
L
L
Ryffel
G U
GU
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D051543:Hepatocyte Nuclear Factor 3-gamma; D051557:Hepatocyte Nuclear Factor 4; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins; D016133:Polymerase Chain Reaction; D053284:Polyunsaturated Alkamides; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D013379:Substrate Specificity; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; D004967:Estrogens; C496501:Foxa1 protein, rat; C496504:Foxa2 protein, rat; C496507:Foxa3 protein, rat; D051538:Hepatocyte Nuclear Factor 1-alpha; D051541:Hepatocyte Nuclear Factor 3-alpha; D051557:Hepatocyte Nuclear Factor 4; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D010750:Phosphoproteins; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D014157:Transcription Factors; D013629:Tamoxifen; D051537:Hepatocyte Nuclear Factor 1; D051543:Hepatocyte Nuclear Factor 3-gamma; D051542:Hepatocyte Nuclear Factor 3-beta; D051539:Hepatocyte Nuclear Factor 1-beta; C016601:afimoxifene; D004958:Estradiol; D004054:Diethylstilbestrol; C051781:ICI 164384