ESTROGEN-INDUCIBLE DERIVATIVES OF HEPATOCYTE NUCLEAR FACTOR-IV, HEPATOCYTE NUCLEAR FACTOR-III AND LIVER FACTOR B1 ARE DIFFERENTLY AFFECTED BY PURE AND PARTIAL ANTIESTROGENS

The tissue-specific transcription factors of the hepatocyte nuclear fa ctor-4 (HNF4), hepatocyte nuclear factor-3 (HNF3), and liver factor B1 (LFB1) families are thought to play a role in the development of inte rnal organs and in the tissue-specific expression of many distinct gen es. We have now constructed derivatives of these proteins by introduci ng the hormone-binding domain of the estrogen receptor and show that i n transient transfections these chimeric proteins act as estrogen-indu cible transcription factors with the DNA sequence specificity of the o riginal factors. These chimeric transcription factors are differently affected by the partial estrogen antagonist 4-hydroxytamoxifen and the pure antiestrogen n-butyl-11-(3,17-dihydroxy-estra-1,3,5(10)-trien-7 alpha-yl)N- methyl-undecamide (ICI 164384); 4-hydroxytamoxifen activat es, at least partially, all the chimeric factors and the estrogen rece ptor, while ICI 164384 surprisingly activates the transcription factor s derived from HNF3 and LFB1 and inhibits only the estrogen receptor a nd the HNF4 derivative. Together with the DNA-sequence-binding specifi city, the different response to estrogen and anti-estrogens makes our estrogen receptor fusion proteins useful tools for the investigation o f the roles of HNF4, HNF3 and LFB1 in gene expression, differentiation and developmental processes.