HNF-3�, C/EBP�, and HNF-4 Act in Synergy to Enhance Transcription of the Human Apolipoprotein B Gene in Intestinal Cells

Antes, Travis J.; Levy-Wilson, Beatriz
February 2001
DNA & Cell Biology;Feb2001, Vol. 20 Issue 2, p67
Academic Journal
Recently, we identified a 315-bp intestinal enhancer (IE), localized over 55 kb upstream from the transcriptional start of the human apolipoprotein B (apoB) gene, that confers expression of human apoB transgenes in the intestines of mice. Four functional binding sites for the intestine-enriched transcription factors hepatocyte nuclear factor (HNF)-3�, CAAT enhancer binding protein (C/EBP)�, and HNF-4 were demonstrated within the 315-bp IE. In this report, we extend these earlier studies and examine the relative contributions of these three transcription factors to the activity of the enhancer as well as their mechanism of interaction with one another. Cotransfection experiments with the expression vectors for HNF-3�, C/EBP�, and HNF-4 revealed that HNF-3� bound to Site 1, C/EBP� bound to Site 2, and HNF-4 bound to Site 3 within the 315-bp IE and that the sites act synergistically to enhance intestinal expression of apoB. Each one of these four binding sites was mutated, and mutant constructs were transfected into intestine-derived CaCo-2 cells to evaluate the role of each of these binding sites in enhancer activity. The results of the mutagenesis experiments confirmed that the HNF-3� and HNF-4 sites are most important for the enhancer activity, followed by C/EBP� Site 2. All three factors bound to Sites 1, 2, and 3 must act synergistically for optimal activity of the apoB IE.


Related Articles

  • LXR-Agonists Regulate ApoM Expression Differentially in Liver and Intestine. Calayir, Emine; Becker, Tatjana M.; Kartzer, Adelheid; Ebner, Birgit; Panzenb�ck, Ute; Stefujl, Jasminka; Kostner, Gerhard M. // Current Pharmaceutical Biotechnology;Dec2008, Vol. 9 Issue 6, p516 

    Apolipoprotein M (apoM) has been suggested to play a role in reverse cholesterol transport. Here we studied the influence of liver X-receptor (LXR) agonist on the transcriptional regulation of apoM. Studies were performed in murine liver and intestinal mucosal cells in vivo and in human...

  • Histone deacetylase interacts directly with DNA topoisomerase II. Tsai, Shih-Chang; Valkov, Nikola; Yang, Wen-Ming; Gump, Jana; Sullivan, Daniel; Seto, Edward // Nature Genetics;Nov2000, Vol. 26 Issue 3, p349 

    Histone deacetylases (HDACs) modify nucleosomal histones, have a key role in the regulation of gene transcription, and may be involved in cell-cycle regulation, differentiation and human cancer. Purified recombinant human HDAC1 protein was used to screen a cDNA expression library, and one of the...

  • Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Mangeat, Bastien; Turelli, Priscilla; Caron, Gersende; Friedli, Marc; Perrin, Luc; Trono, Didier // Nature;7/3/2003, Vol. 424 Issue 6944, p99 

    Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to...

  • A Bifunctional Regulatory Element of the Human ApoA-I Gene Responsive to a Distal Enhancer. Jones, Daniel R.; Leffak, Michael // DNA & Cell Biology;Feb99, Vol. 18 Issue 2, p107 

    Promoter elements located up to 2 kb upstream of the apolipoprotein A-I (apoA-I) gene are necessary for apoA-I expression in liver and intestine cells in tissue culture. In transgenic mice, a distal enhancer located between the apoA-IV and apoC-III genes is additionally necessary for...

  • Commensal Streptococcus salivarius Modulates PPARγ Transcriptional Activity in Human Intestinal Epithelial Cells. Couvigny, Benoît; de Wouters, Tomas; Kaci, Ghalia; Jacouton, Elsa; Delorme, Christine; Doré, Joël; Renault, Pierre; Blottière, Hervé M.; Guédon, Eric; Lapaque, Nicolas // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    The impact of commensal bacteria in eukaryotic transcriptional regulation has increasingly been demonstrated over the last decades. A multitude of studies have shown direct effects of commensal bacteria from local transcriptional activity to systemic impact. The commensal bacterium Streptococcus...

  • The mechanisms of action of interleukin-1 on rabbit intestinal epithelial cells. Homaidan, Fadia R.; Zhao, Liming; Chakroun, Iman; Martin, Carla A.; Burakoff, Robert // Mediators of Inflammation;Aug99, Vol. 8 Issue 4/5, p189 

    INTERLEUKIN-1 (IL-1) is an inflammatory mediator that increases Cl[sup -] secretion in intestinal epithelial cells. To identify the signal transduction pathway(s) involved in IL-1's action, cells were treated with IL-1 and the levels of cyclooxygenase (COX) enzymes, prostaglandin E[sub 2]...

  • The Role of Apolipoprotein AIV on the Control of Food Intake. Qin, Xiaofa; Tso, Patrick // Current Drug Targets;Mar2005, Vol. 6 Issue 2, p145 

    Apolipoprotein AIV (apo AIV) is a protein synthesized by the human intestine. The synthesis and secretion of apo AIV are stimulated by fat absorption. In 1992, Fujimoto et al. [1] first demonstrated that apo AIV is a satiety signal secreted by the small intestine following the ingestion of a...

  • A single-nucleotide polymorphism in the human p27kip1 gene (-838C>A) affects basal promoter activity and the risk of myocardial infarction. González, Pelayo; Díez-Juan, Antonio; Coto, Eliecer; Álvarez, Victoria; Reguero, Julian R.; Batalla, Alberto; Andrés, Vicente // BMC Biology;2004, Vol. 2, p1 

    Background: Excessive proliferation of vascular smooth muscle cells and leukocytes within the artery wall is a major event in the development of atherosclerosis. The growth suppressor p27kip1 associates with several cyclin-dependent kinase/cyclin complexes, thereby abrogating their capacity to...

  • Association Between Alzheimer Disease and the −491T Allele of Regulatory Region Polymorphism of Apolipoprotein E in a Tunisian Population. Achouri-Rassas, Afef; Hadj Fredj, Sondes; Mrabet Khiari, Hela; Bibi, Amina; Siala, Hajer; Mrabet, Amel; Messaoud, Taieb // Neurochemical Research;Feb2014, Vol. 39 Issue 2, p244 

    The apolipoprotein E ( APOE) is a well-established risk factor for late-onset Alzheimer's disease (AD). Several studies have attempted to confirm the association between the polymorphism located at position −491 in the transcriptional regulatory region of the APOE gene and AD. We examined...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics