Orphan Receptor Hepatocyte Nuclear Factor-4 Antagonizes Estrogen Receptor α-Mediated Induction of Human Coagulation Factor XII Gene1

Autor:	Antonella Farsetti, Simona Nanni, M Andreoli, Michela Narducci, Ada Sacchi, Fabiola Moretti, Alfredo Pontecorvi, Silvia Misiti
Rok vydání:	1998
Předmět:	Orphan receptor Hormone response element medicine.medical_specialty Estrogen receptor Biology Molecular biology Neuron-derived orphan receptor 1 Endocrinology Hepatocyte nuclear factor 4 Internal medicine medicine Estrogen-related receptor gamma Estrogen receptor alpha Estrogen receptor beta
Zdroj:	Endocrinology. 139:4581-4589
ISSN:	1945-7170 0013-7227
DOI:	10.1210/endo.139.11.6299
Popis:	Factor XII (FXII) is a liver-specific zymogen involved in the regulation of hemostasis, particularly in the activation of fibrinolysis. Transcription of the FXII gene is stimulated by estrogens through specific interaction of the estrogen receptor α (ERα) with an estrogen response element present on FXII promoter. Interestingly, the magnitude of ERα induction in liver HepG2 cells is much lower than in NIH3T3 fibroblasts, suggesting that cell-specific factors may modulate ERα-dependent trans-activation. Comparative footprinting analysis of FXII promoter (from nucleotides -181 to +49) in liver vs. non-liver cell environments allowed identification of four deoxyribonuclease I-protected sites only in the presence of HepG2 nuclear extracts. Computerized homology search identified sites III and IV as consensus binding sequences for the liver-enriched transcription factor hepatocyte nuclear factor-4 (HNF-4), formerly an orphan receptor belonging to the superfamily of steroid/thyroid hormone nuclear receptors. In...
Databáze:	OpenAIRE
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