HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harnish, D. C. Articles by Karathanasis, S. K. Search for Related Content PubMed PubMed Citation Articles by Harnish, D. C. Articles by Karathanasis, S. K. Social Bookmarking                      What's this?

Volume 271, Number 23, Issue of June 7, 1996 pp. 13621-13628
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Control of Apolipoprotein AI Gene Expression through Synergistic Interactions between Hepatocyte Nuclear Factors 3 and 4

(Received for publication, January 29, 1996, and in revised form, March 22, 1996)

Douglas C. Harnish , Sohail Malik , Edward Kilbourne , Robert Costa and Sotirios K. Karathanasis

From the  Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, New York 10965 and the  Department of Biochemistry, University of Illinois at Chicago, Chicago, Illinois 60612-7334

Apolipoprotein AI (apoAI) gene expression in liver depends on synergistic interactions between transcription factors bound to three distinct sites (A, B, and C) within a hepatocyte-specific enhancer in the 5-flanking region of the gene. In this study, we showed that a segment spanning sites A and B retains substantial levels of enhancer activity in hepatoblastoma HepG2 cells and that sites A and B are occupied by the liver-enriched hepatocyte nuclear factors (HNFs) 4 and 3, respectively, in these cells. In non-hepatic CV-1 cells, HNF-4 and HNF-3 activated this minimal enhancer synergistically. This synergy was dependent upon simultaneous binding of these factors to their cognate sites, but it was not due to cooperativity in DNA binding. Separation of these sites by varying helical turns of DNA did not affect simultaneous binding of HNF-3 and HNF-4 nor did it influence their functional synergy. The synergy was, however, dependent upon the cell type used for functional analysis. In addition, this synergy was further potentiated by estrogen treatment of cells cotransfected with the estrogen receptor. These data indicate that a cell type-restricted intermediary factor jointly recruited by HNF-4 and HNF-3 participates in activation of the apoAI enhancer in liver cells and suggest that the activity of this factor is regulated by estrogen.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Nock, J. M. Ascano, T. Jones, M. J. Barrero, N. Sugiyama, M. Tomita, Y. Ishihama, and S. Malik Identification of DNA-dependent Protein Kinase as a Cofactor for the Forkhead Transcription Factor FoxA2 J. Biol. Chem., July 24, 2009; 284(30): 19915 - 19926. [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]

				P. Minoo, L. Hu, N. Zhu, Z. Borok, S. Bellusci, J. Groffen, D. Kardassis, and C. Li SMAD3 prevents binding of NKX2.1 and FOXA1 to the SpB promoter through its MH1 and MH2 domains Nucleic Acids Res., January 17, 2008; 36(1): 179 - 188. [Abstract] [Full Text] [PDF]

				J. Rhee, H. Ge, W. Yang, M. Fan, C. Handschin, M. Cooper, J. Lin, C. Li, and B. M. Spiegelman Partnership of PGC-1{alpha} and HNF4{alpha} in the Regulation of Lipoprotein Metabolism J. Biol. Chem., May 26, 2006; 281(21): 14683 - 14690. [Abstract] [Full Text] [PDF]

				X. Prieur, F. G. Schaap, H. Coste, and J. C. Rodriguez Hepatocyte Nuclear Factor-4{alpha} Regulates the Human Apolipoprotein AV Gene: Identification of a Novel Response Element and Involvement in the Control by Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha}, AMP-Activated Protein Kinase, and Mitogen-Activated Protein Kinase Pathway Mol. Endocrinol., December 1, 2005; 19(12): 3107 - 3125. [Abstract] [Full Text] [PDF]

				A. Rada-Iglesias, O. Wallerman, C. Koch, A. Ameur, S. Enroth, G. Clelland, K. Wester, S. Wilcox, O. M. Dovey, P. D. Ellis, et al. Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays Hum. Mol. Genet., November 15, 2005; 14(22): 3435 - 3447. [Abstract] [Full Text] [PDF]

				S. Lamon-Fava and D. Micherone Regulation of apoA-I gene expression: mechanism of action of estrogen and genistein J. Lipid Res., January 1, 2004; 45(1): 106 - 112. [Abstract] [Full Text] [PDF]

				J. Y. L. Chiang Bile Acid Regulation of Gene Expression: Roles of Nuclear Hormone Receptors Endocr. Rev., August 1, 2002; 23(4): 443 - 463. [Abstract] [Full Text] [PDF]

				L. Cui, N. W. Schoene, L. Zhu, J. C. Fanzo, A. Alshatwi, and K. Y. Lei Zinc depletion reduced Egr-1 and HNF-3beta expression and apolipoprotein A-I promoter activity in Hep G2 cells Am J Physiol Cell Physiol, August 1, 2002; 283(2): C623 - C630. [Abstract] [Full Text] [PDF]

				Y. Inoue, G. P. Hayhurst, J. Inoue, M. Mori, and F. J. Gonzalez Defective Ureagenesis in Mice Carrying a Liver-specific Disruption of Hepatocyte Nuclear Factor 4alpha (HNF4alpha ). HNF4alpha REGULATES ORNITHINE TRANSCARBAMYLASE IN VIVO J. Biol. Chem., July 5, 2002; 277(28): 25257 - 25265. [Abstract] [Full Text] [PDF]

				C. Hu and D. H. Perlmutter Cell-specific involvement of HNF-1beta in alpha 1-antitrypsin gene expression in human respiratory epithelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L757 - L765. [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]

				G. P. Hayhurst, Y.-H. Lee, G. Lambert, J. M. Ward, and F. J. Gonzalez Hepatocyte Nuclear Factor 4{alpha} (Nuclear Receptor 2A1) Is Essential for Maintenance of Hepatic Gene Expression and Lipid Homeostasis Mol. Cell. Biol., February 15, 2001; 21(4): 1393 - 1403. [Abstract] [Full Text]

				F. M. Rausa, Y. Tan, H. Zhou, K. W. Yoo, D. B. Stolz, S. C. Watkins, R. R. Franks, T. G. Unterman, and R. H. Costa Elevated Levels of Hepatocyte Nuclear Factor 3beta in Mouse Hepatocytes Influence Expression of Genes Involved in Bile Acid and Glucose Homeostasis Mol. Cell. Biol., November 1, 2000; 20(21): 8264 - 8282. [Abstract] [Full Text]

				S. Lamon-Fava Genistein Activates Apolipoprotein A-I Gene Expression in the Human Hepatoma Cell Line Hep G2 J. Nutr., October 1, 2000; 130(10): 2489 - 2492. [Abstract] [Full Text]

				S. Santamarina-Fojo, K. Peterson, C. Knapper, Y. Qiu, L. Freeman, J.-F. Cheng, J. Osorio, A. Remaley, X.-P. Yang, C. Haudenschild, et al. Complete genomic sequence of the human ABCA1 gene: Analysis of the human and mouse ATP-binding cassette A promoter PNAS, July 5, 2000; 97(14): 7987 - 7992. [Abstract] [Full Text] [PDF]

				J. Li, G. Ning, and S. A. Duncan Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha Genes & Dev., February 15, 2000; 14(4): 464 - 474. [Abstract] [Full Text]

				S. Lamon-Fava, J. M. Ordovas, and E. J. Schaefer Estrogen Increases Apolipoprotein (Apo) A-I Secretion in Hep G2 Cells by Modulating Transcription of the Apo A-I Gene Promoter Arterioscler. Thromb. Vasc. Biol., December 1, 1999; 19(12): 2960 - 2965. [Abstract] [Full Text] [PDF]

				Q. Shi, T. A. Black, K. W. Gross, and C. D. Sigmund Species-Specific Differences in Positive and Negative Regulatory Elements in the Renin Gene Enhancer Circ. Res., September 17, 1999; 85(6): 479 - 488. [Abstract] [Full Text] [PDF]

				T. Nakamura, A. Fox-Robichaud, R. Kikkawa, A. Kashiwagi, H. Kojima, M. Fujimiya, and N. C. W. Wong Transcription factors and age-related decline in apolipoprotein A-I expression J. Lipid Res., September 1, 1999; 40(9): 1709 - 1718. [Abstract] [Full Text]

				A. Matsunaga, J. Sasaki, H. Han, W. Huang, M. Kugi, T. Koga, S. Ichiki, T. Shinkawa, and K. Arakawa Compound Heterozygosity for an Apolipoprotein A1 Gene Promoter Mutation and a Structural Nonsense Mutation With Apolipoprotein A1 Deficiency Arterioscler. Thromb. Vasc. Biol., February 1, 1999; 19(2): 348 - 355. [Abstract] [Full Text] [PDF]

				D. M. Dean, R. R. Berger, and M. M. Sanders A Winged-Helix Family Member Is Involved in a Steroid Hormone-Triggered Regulatory Circuit Endocrinology, December 1, 1998; 139(12): 4967 - 4975. [Abstract] [Full Text] [PDF]

				M. Crestani, A. Sadeghpour, D. Stroup, G. Galli, and J. Y. L. Chiang Transcriptional activation of the cholesterol 7{alpha}-hydroxylase gene (CYP7A) by nuclear hormone receptors J. Lipid Res., November 1, 1998; 39(11): 2192 - 2200. [Full Text]

				C. Gregori, A. Porteu, S. Lopez, A. Kahn, and A.-L. Pichard Characterization of the Aldolase B Intronic Enhancer J. Biol. Chem., September 25, 1998; 273(39): 25237 - 25243. [Abstract] [Full Text] [PDF]

				S.-K. Lee, H.-S. Choi, M.-R. Song, M.-O. Lee, and J. W. Lee Estrogen Receptor, a Common Interaction Partner for a Subset of Nuclear Receptors Mol. Endocrinol., August 1, 1998; 12(8): 1184 - 1192. [Abstract] [Full Text]

				D. C. Harnish, M. J. Evans, M. S. Scicchitano, R. A. Bhat, and S. K. Karathanasis Estrogen Regulation of the Apolipoprotein AI Gene Promoter through Transcription Cofactor Sharing J. Biol. Chem., April 10, 1998; 273(15): 9270 - 9278. [Abstract] [Full Text] [PDF]

				K. Prufer, A. Racz, G. C. Lin, and J. Barsony Dimerization with Retinoid X Receptors Promotes Nuclear Localization and Subnuclear Targeting of Vitamin D Receptors J. Biol. Chem., December 22, 2000; 275(52): 41114 - 41123. [Abstract] [Full Text] [PDF]

				J.-C. Wang, M. Waltner-Law, K. Yamada, H. Osawa, S. Stifani, and D. K. Granner Transducin-like Enhancer of Split Proteins, the Human Homologs of Drosophila Groucho, Interact with Hepatic Nuclear Factor 3beta J. Biol. Chem., June 9, 2000; 275(24): 18418 - 18423. [Abstract] [Full Text] [PDF]