Cell Growth & Differentiation, Vol 6, Issue 7 879-890, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Cytokine regulation of the liver transcription factor hepatocyte nuclear factor-3 beta is mediated by the C/EBP family and interferon regulatory factor 1

U Samadani, A Porcella, L Pani, PF Johnson, JB Burch, R Pine and RH Costa
Department of Biochemistry, University of Illinois at Chicago 60612-7334, USA.

Three distinct hepatocyte nuclear factor-3 (HNF-3) proteins (alpha, beta, and gamma) regulate the transcription of numerous liver-enriched genes. The HNF-3 proteins bind DNA via a homologous winged helix motif common to a number of proteins known to be critical for determination events in embryogenesis. We have demonstrated previously that two binding sites in the -184 HNF-3 beta promoter are recognized by widely distributed factors and that there is also a critical autoregulatory site, we identified a binding site for a cell-specific factor, LF-H3 beta, that may function in restricting HNF-3 beta gene expression to hepatocytes. Our present study demonstrates that members of the C/EBP and proline and acidic amino acid-rich subfamilies of basic region leucine zipper transcription factors bind the LF-H3 beta site, and cotransfection of HepG2 cells shows that these factors are able to activate an HNF-3 beta promoter reporter construct. The LF-H3 beta-C/EBP binding sequence also confers HNF-3 beta promoter stimulation in response to interleukin (IL)-1 and IL-6. Upstream of this HNF-3 beta proximal promoter region, an IFN-stimulated response element core sequence (-231 to -210) was found that mediates transcriptional induction by IFN-gamma but not IFN-alpha. Gel mobility supershift assay demonstrates that an IFN-gamma-induced protein-DNA complex is disrupted by an antibody specific for interferon regulatory factor-1/interferon-stimulated gene factor-2. Consistent with this finding, we observed that IFN-gamma induction requires ongoing protein synthesis. Surprisingly, the effect of the three cytokines (IL-1, IL-6, and IFN-gamma) in combination as assayed by the same model is not synergistic. HNF-3beta joins the C/EBP family on the list of liver-enriched transcription factors, the expression of which is modulated by cytokines.

This article has been cited by other articles:

				K. Kotlo, D. E. Hughes, V. L.M. Herrera, N. Ruiz-Opazo, R. H. Costa, R. B. Robey, and R. S. Danziger Functional Polymorphism of the Anpep Gene Increases Promoter Activity in the Dahl Salt-Resistant Rat Hypertension, March 1, 2007; 49(3): 467 - 472. [Abstract] [Full Text] [PDF]

				E. W. Abrams and D. J. Andrew CrebA regulates secretory activity in the Drosophila salivary gland and epidermis Development, June 15, 2005; 132(12): 2743 - 2758. [Abstract] [Full Text] [PDF]

				B. Halmos, D. S. Basseres, S. Monti, F. D'Alo, T. Dayaram, K. Ferenczi, B. J. Wouters, C. S. Huettner, T. R. Golub, and D. G. Tenen A Transcriptional Profiling Study of CCAAT/Enhancer Binding Protein Targets Identifies Hepatocyte Nuclear Factor 3{beta} as a Novel Tumor Suppressor in Lung Cancer Cancer Res., June 15, 2004; 64(12): 4137 - 4147. [Abstract] [Full Text] [PDF]

				F. M. Rausa, Y. Tan, and R. H. Costa Association between Hepatocyte Nuclear Factor 6 (HNF-6) and FoxA2 DNA Binding Domains Stimulates FoxA2 Transcriptional Activity but Inhibits HNF-6 DNA Binding Mol. Cell. Biol., January 15, 2003; 23(2): 437 - 449. [Abstract] [Full Text] [PDF]

				P. L. Ramsay, Z. Luo, S. M. Magdaleno, S. K. Whitbourne, X. Cao, M. S. Park, S. E. Welty, L.-Y. Yu-Lee, and F. J. DeMayo Transcriptional regulation of CCSP by interferon-gamma in vitro and in vivo Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L108 - L118. [Abstract] [Full Text] [PDF]

				H. Schrem, J. Klempnauer, and J. Borlak Liver-Enriched Transcription Factors in Liver Function and Development. Part I: The Hepatocyte Nuclear Factor Network and Liver-Specific Gene Expression Pharmacol. Rev., March 1, 2002; 54(1): 129 - 158. [Abstract] [Full Text] [PDF]

				R. H. Costa, V. V. Kalinichenko, and L. Lim Transcription factors in mouse lung development and function Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L823 - L838. [Abstract] [Full Text] [PDF]

				L. Xu, L. Hui, S. Wang, J. Gong, Y. Jin, Y. Wang, Y. Ji, X. Wu, Z. Han, and G. Hu Expression Profiling Suggested a Regulatory Role of Liver-enriched Transcription Factors in Human Hepatocellular Carcinoma Cancer Res., April 1, 2001; 61(7): 3176 - 3181. [Abstract] [Full Text]

				M. Rastegar, G. G. Rousseau, and F. P. Lemaigre CCAAT/Enhancer-Binding Protein-{alpha} Is a Component of the Growth Hormone-Regulated Network of Liver Transcription Factors Endocrinology, May 1, 2000; 141(5): 1686 - 1692. [Abstract] [Full Text] [PDF]

				A Bailly, G Spath, V Bender, and M. Weiss Phenotypic effects of the forced expression of HNF4 and HNF1alpha are conditioned by properties of the recipient cell J. Cell Sci., January 8, 1998; 111(16): 2411 - 2421. [Abstract] [PDF]

				L. Lim, H. Zhou, and R. H. Costa The winged helix transcription factor HFH-4 is expressed during choroid plexus epithelial development in the mouse embryo PNAS, April 1, 1997; 94(7): 3094 - 3099. [Abstract] [Full Text] [PDF]

				S. Lin, M. Lin, P Horvath, K. Reddy, and R. Storti PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes Development, January 11, 1997; 124(22): 4685 - 4696. [Abstract] [PDF]

				J. Sutton, R. Costa, M. Klug, L. Field, D. Xu, D. A. Largaespada, C. F. Fletcher, N. A. Jenkins, N. G. Copeland, M. Klemsz, et al. Genesis, a Winged Helix Transcriptional Repressor with Expression Restricted to Embryonic Stem Cells J. Biol. Chem., September 20, 1996; 271(38): 23126 - 23133. [Abstract] [Full Text] [PDF]