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Cytokine regulation of the liver transcription factor hepatocyte nuclear factor-3 beta is mediated by the C/EBP family and interferon regulatory factor 1.
Cell Growth Differ. 1995 Jul; 6(7):879-90.CG

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry, University of Illinois at Chicago 60612-7334, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7547510

Citation

Samadani, U, et al. "Cytokine Regulation of the Liver Transcription Factor Hepatocyte Nuclear Factor-3 Beta Is Mediated By the C/EBP Family and Interferon Regulatory Factor 1." Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, vol. 6, no. 7, 1995, pp. 879-90.
Samadani U, Porcella A, Pani L, et al. Cytokine regulation of the liver transcription factor hepatocyte nuclear factor-3 beta is mediated by the C/EBP family and interferon regulatory factor 1. Cell Growth Differ. 1995;6(7):879-90.
Samadani, U., Porcella, A., Pani, L., Johnson, P. F., Burch, J. B., Pine, R., & Costa, R. H. (1995). Cytokine regulation of the liver transcription factor hepatocyte nuclear factor-3 beta is mediated by the C/EBP family and interferon regulatory factor 1. Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, 6(7), 879-90.
Samadani U, et al. Cytokine Regulation of the Liver Transcription Factor Hepatocyte Nuclear Factor-3 Beta Is Mediated By the C/EBP Family and Interferon Regulatory Factor 1. Cell Growth Differ. 1995;6(7):879-90. PubMed PMID: 7547510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokine regulation of the liver transcription factor hepatocyte nuclear factor-3 beta is mediated by the C/EBP family and interferon regulatory factor 1. AU - Samadani,U, AU - Porcella,A, AU - Pani,L, AU - Johnson,P F, AU - Burch,J B, AU - Pine,R, AU - Costa,R H, PY - 1995/7/1/pubmed PY - 1995/7/1/medline PY - 1995/7/1/entrez SP - 879 EP - 90 JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research JO - Cell Growth Differ VL - 6 IS - 7 N2 - 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. SN - 1044-9523 UR - https://www.unboundmedicine.com/medline/citation/7547510/Cytokine_regulation_of_the_liver_transcription_factor_hepatocyte_nuclear_factor_3_beta_is_mediated_by_the_C/EBP_family_and_interferon_regulatory_factor_1_ L2 - http://cgd.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7547510 DB - PRIME DP - Unbound Medicine ER -