Nucleic Acids Research, 2000, Vol. 28, No. 3 800-808
© 2000 Oxford University Press
Activation of c-myc promoter P1 by immunoglobulin 
gene enhancers in Burkitt lymphoma: functional characterization of the intron enhancer motifs B, E box 1 and E box 2, and of the 3' enhancer motif PU
GSF–National Research Center for Environment and Health, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistraße 25, D-81377 Munich, Germany
Deregulated expression of the proto-oncogene c-myc in Burkitt lymphoma (BL) cells carrying a t(2;8) translocation is mediated by a synergistic interaction of the translocated immunoglobulin (Ig) 
gene intron (Ei) and 3' (E3') enhancers and characterized by a strong activation of the promoter P1. We have investigated the functional role of distinct enhancer sequence motifs in P1 activation on both minichromosomes and reporter gene constructs. Stable and transient transfections of BL cells revealed critical roles of the Ei and E3' elements B and PU, respectively. Joint mutation of B and PU completely abolished P1 activity, implying that an interaction of B- and PU-binding factors is essential for the enhancer synergism. Mutation of the E box 1 and E box 2 motifs markedly decreased P1 activity in transient but not in stable transfection experiments. Co-expression of the NF-B subunit p65(RelA) and Sp1, an essential factor for P1 transcription, in Drosophila melanogaster SL2 cells synergistically enhanced promoter activity. Our results support a model which proposes cross-talk between promoter and enhancer binding factors as the basic mechanism for enhancer-mediated c-myc activation in BL cells.
* To whom correspondence should be addressed at present address: Max-Planck-Institute for Biochemistry, Department for Membrane Biochemistry, Am Klopferspitz 18a, D-82152 Martinsried, Germany. Tel: +49 89 8578 2368; Fax: +49 89 8578 2368; Email: wittekin@biochem.mpg.de Present addresses: Konstanze Hörtnagel, Ludwig-Maximilians Universität, Department of Medical Genetics, Goethestraße 29, D-80336 Munich, Germany Axel Polack, GSF–National Research Center for Environment and Health, Scientific Technical Department, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Shishodia and B. B. Aggarwal Guggulsterone Inhibits NF-{kappa}B and I{kappa}B{alpha} Kinase Activation, Suppresses Expression of Anti-apoptotic Gene Products, and Enhances Apoptosis J. Biol. Chem., November 5, 2004; 279(45): 47148 - 47158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Hu, M. Arcinas, and L. M. Boxer A Myc-associated Zinc Finger Protein-related Factor Binding Site Is Required for the Deregulation of c-myc Expression by the Immunoglobulin Heavy Chain Gene Enhancers in Burkitt's Lymphoma J. Biol. Chem., March 15, 2002; 277(12): 9819 - 9824. [Abstract] [Full Text] [PDF]
|
|