An enhancer element 6 kb upstream of the mouse HNF4 alpha 1 promoter is activated by glucocorticoids and liver-enriched transcription factors

Citation
A. Bailly et al., An enhancer element 6 kb upstream of the mouse HNF4 alpha 1 promoter is activated by glucocorticoids and liver-enriched transcription factors, NUCL ACID R, 29(17), 2001, pp. 3495-3505
Citations number
63
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEIC ACIDS RESEARCH
ISSN journal
03051048 → ACNP
Volume
29
Issue
17
Year of publication
2001
Pages
3495 - 3505
Database
ISI
SICI code
0305-1048(20010901)29:17<3495:AEE6KU>2.0.ZU;2-1
Abstract
We have characterized a 700 bp enhancer element around -6 kb relative to th e HNF4 alpha1 transcription start. This element increases activity and conf ers glucocorticoid induction to a heterologous as well as the homologous pr omoters in differentiated hepatoma cells and is transactivated by HNF4 alph a1, HNF4 alpha7, HNF1 alpha and HNF1 beta in dedifferentiated hepatoma cell s. A 240 bp sub-region conserves basal and hormone-induced enhancer activit y. It contains HNF1, HNF4, HNF3 and C/EBP binding sites as shown by DNase I footprinting and electrophoretic mobility shift assays using nuclear extra cts and/or recombinant HNF1 alpha and HNF4 alpha1. Mutation analyses showed that the HNF1 site is essential for HNF1 alpha transactivation and is requ ired for full basal enhancer activity, as is the C/EBP site. Glucocorticoid response element consensus sites which overlap the C/EBP, HNF4 and HNF3 si tes are crucial for optimal hormonal induction. We present a model that acc ounts for weak expression of HNF4 alpha1 in the embryonic liver and strong expression in the newborn/adult liver via the binding sites identified in t he enhancer.