Nucleic Acids Research, 2001, Vol. 29, No. 17 3495-3505
© 2001 Oxford University Press
An enhancer element 6 kb upstream of the mouse HNF4
1 promoter is activated by glucocorticoids and liver-enriched transcription factors
Unité de Génétique de la Différenciation, FRE 2364 du CNRS, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France
We have characterized a 700 bp enhancer element around –6 kb relative to the HNF4
1 transcription start. This element increases activity and confers glucocorticoid induction to a heterologous as well as the homologous promoters in differentiated hepatoma cells and is transactivated by HNF41, HNF47, HNF1 and HNF1ß in dedifferentiated hepatoma cells. A 240 bp sub-region conserves basal and hormone-induced enhancer activity. It contains HNF1, HNF4, HNF3 and C/EBP binding sites as shown by DNase I footprinting and electrophoretic mobility shift assays using nuclear extracts and/or recombinant HNF1 and HNF41. Mutation analyses showed that the HNF1 site is essential for HNF1 transactivation and is required for full basal enhancer activity, as is the C/EBP site. Glucocorticoid response element consensus sites which overlap the C/EBP, HNF4 and HNF3 sites are crucial for optimal hormonal induction. We present a model that accounts for weak expression of HNF41 in the embryonic liver and strong expression in the newborn/adult liver via the binding sites identified in the enhancer.
* To whom correspondence should be addressed. Tel: +33 1 45 68 85 00; Fax: +33 1 40 61 32 31; Email: mweiss{at}pasteur.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. S. Barr, R. L. Dvoskin, Q. Yuan, R. H. Lipsky, M. Gupte, X. Hu, Z. Zhou, M. L. Schwandt, S. G. Lindell, M. McKee, et al. CRH Haplotype as a Factor Influencing Cerebrospinal Fluid Levels of Corticotropin-Releasing Hormone, Hypothalamic-Pituitary-Adrenal Axis Activity, Temperament, and Alcohol Consumption in Rhesus Macaques Arch Gen Psychiatry, August 1, 2008; 65(8): 934 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Wederell, M. Bilenky, R. Cullum, N. Thiessen, M. Dagpinar, A. Delaney, R. Varhol, Y. Zhao, T. Zeng, B. Bernier, et al. Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing Nucleic Acids Res., August 1, 2008; 36(14): 4549 - 4564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gates Goodyer, Z. Rhani, and H. Zheng Expression of the Hepatic Specific V1 Messenger Ribonucleic Acid of the Human Growth Hormone Receptor Gene Is Regulated by Hepatic Nuclear Factor (HNF)-4{alpha}2 and HNF-4{alpha}8 Mol. Endocrinol., February 1, 2008; 22(2): 485 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Scheving, R. Buchanan, M. A. Krause, X. Zhang, M. C. Stevenson, and W. E. Russell Dexamethasone modulates ErbB tyrosine kinase expression and signaling through multiple and redundant mechanisms in cultured rat hepatocytes Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G552 - G559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hatzis, I. Kyrmizi, and I. Talianidis Mitogen-Activated Protein Kinase-Mediated Disruption of Enhancer-Promoter Communication Inhibits Hepatocyte Nuclear Factor 4{alpha} Expression. Mol. Cell. Biol., October 1, 2006; 26(19): 7017 - 7029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Qadri, M. Iwahashi, G. A. Kullak-Ublick, and F. R. Simon Hepatocyte Nuclear Factor (HNF) 1 and HNF4 Mediate Hepatic Multidrug Resistance Protein 2 Up-Regulation during Hepatitis C Virus Gene Expression Mol. Pharmacol., August 1, 2006; 70(2): 627 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Briancon, A. Bailly, F. Clotman, P. Jacquemin, F. P. Lemaigre, and M. C. Weiss Expression of the {alpha}7 Isoform of Hepatocyte Nuclear Factor (HNF) 4 Is Activated by HNF6/OC-2 and HNF1 and Repressed by HNF4{alpha}1 in the Liver J. Biol. Chem., August 6, 2004; 279(32): 33398 - 33408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Wiwi, M. Gupte, and D. J. Waxman Sexually Dimorphic P450 Gene Expression in Liver-Specific Hepatocyte Nuclear Factor 4{alpha}-Deficient Mice Mol. Endocrinol., August 1, 2004; 18(8): 1975 - 1987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Gloyn, S. Ellard, M. Shepherd, R. T. Howell, E. M. Parry, A. Jefferson, E. R. Levy, and A. T. Hattersley Maturity-Onset Diabetes of the Young Caused by a Balanced Translocation Where the 20q12 Break Point Results in Disruption Upstream of the Coding Region of Hepatocyte Nuclear Factor-4{alpha} (HNF4A) Gene Diabetes, July 1, 2002; 51(7): 2329 - 2333. [Abstract] [Full Text] [PDF]
|
|