| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print February 20, 2001
J. Biol. Chem, 10.1074/jbc.M100265200
Submitted on January 11, 2001
Revised on February 12, 2001
Accepted on February 20, 2001
Institute of Clinical Molecular Biology and Tumor Genetics, GSF Research Centre, D-81377, Munich
Corresponding Author: eick{at}gsf.de
The proto-oncogene c-myc is transcribed from a dual promoter P1/P2, with transcription initiation sites 160 bp apart. Here we have studied the transcriptional activation of both promoters on chromatin templates. C-myc chromatin was reconstituted on stably transfected, episomal, Epstein-Barr virus-derived vectors in a B cell line. Episomal P1 and P2 promoters showed only basal activity but were strongly inducible by histone deacetylase inhibitors. The effect of promoter mutations on c-myc activity, chromatin structure, and E2F binding was studied. The ME1a1 binding site between P1 and P2 was required for the maintenance of an open chromatin configuration of the dual c-myc promoters. Mutation of this site strongly reduced the sensitivity of the core promoter region of P1/P2 to micrococcal nuclease and prevented binding of pol II at the P2 promoter. In contrast, mutation of the P2 TATA box also abolished binding of pol II at the P2 promoter but did not affect the chromatin structure of the P1/P2 core promoter region. The E2F binding site adjacent to ME1a1 is required for repression of the P2 promoter, but not the P1 promoter, likely by recruitment of histone deacetylase activity. Chromatin precipitation experiments with E2F-specific antibodies revealed binding of E2F-1, E2F-2, and E2F-4 to the E2F site of the c-myc promoter in vivo, if the E2F site was intact. Taken together, the analyses support a model with a functional hierarchy for regulatory elements in the c-myc promoter region: binding of proteins to the ME1a1 site provides a nucleosome-free region of chromatin near the P2 start site, binding of E2F results in transcriptional repression without affecting polymerase recruitment, and the TATA box is required for polymerase recruitment.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Roca and R. T. Franceschi Analysis of transcription factor interactions in osteoblasts using competitive chromatin immunoprecipitation Nucleic Acids Res., March 1, 2008; 36(5): 1723 - 1730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sjottem, C. Rekdal, G. Svineng, S. S. Johnsen, H. Klenow, R. D. Uglehus, and T. Johansen The ePHD protein SPBP interacts with TopBP1 and together they co-operate to stimulate Ets1-mediated transcription Nucleic Acids Res., October 8, 2007; 35(19): 6648 - 6662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lux, H. Albiez, R. D. Chapman, M. Heidinger, M. Meininghaus, R. Brack-Werner, A. Lang, M. Ziegler, T. Cremer, and D. Eick Transition from initiation to promoter proximal pausing requires the CTD of RNA polymerase II Nucleic Acids Res., September 12, 2005; 33(16): 5139 - 5144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Ma, M. J. Chang, R. C. Shah, and E. N. Benveniste Interferon-{gamma}-activated STAT-1{alpha} suppresses MMP-9 gene transcription by sequestration of the coactivators CBP/p300 J. Leukoc. Biol., August 1, 2005; 78(2): 515 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. R. MacLellan, A. Garcia, H. Oh, P. Frenkel, M. C. Jordan, K. P. Roos, and M. D. Schneider Overlapping Roles of Pocket Proteins in the Myocardium Are Unmasked by Germ Line Deletion of p130 plus Heart-Specific Deletion of Rb Mol. Cell. Biol., March 15, 2005; 25(6): 2486 - 2497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Ma, M. J. Chang, R. Shah, J. Adamski, X. Zhao, and E. N. Benveniste Brg-1 Is Required for Maximal Transcription of the Human Matrix Metalloproteinase-2 Gene J. Biol. Chem., October 29, 2004; 279(44): 46326 - 46334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Oshima, T. Nakamura, S. Namiki, E. Okada, K. Tsuchiya, R. Okamoto, M. Yamazaki, T. Yokota, M. Aida, Y. Yamaguchi, et al. Interferon Regulatory Factor 1 (IRF-1) and IRF-2 Distinctively Up-Regulate Gene Expression and Production of Interleukin-7 in Human Intestinal Epithelial Cells Mol. Cell. Biol., July 15, 2004; 24(14): 6298 - 6310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ma, R. C. Shah, M. J. Chang, and E. N. Benveniste Coordination of Cell Signaling, Chromatin Remodeling, Histone Modifications, and Regulator Recruitment in Human Matrix Metalloproteinase 9 Gene Transcription Mol. Cell. Biol., June 15, 2004; 24(12): 5496 - 5509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Carbone, E. McGuffie, S. Napoli, C. E. Flanagan, C. Dembech, U. Negri, F. Arcamone, M. L. Capobianco, and C. V. Catapano DNA binding and antigene activity of a daunomycin-conjugated triplex-forming oligonucleotide targeting the P2 promoter of the human c-myc gene Nucleic Acids Res., April 30, 2004; 32(8): 2396 - 2410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. McConnell, N. Chevallier, W. Berkofsky-Fessler, J. M. Giltnane, R. B. Malani, L. M. Staudt, and J. D. Licht Growth Suppression by Acute Promyelocytic Leukemia-Associated Protein PLZF Is Mediated by Repression of c-myc Expression Mol. Cell. Biol., December 15, 2003; 23(24): 9375 - 9388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Baluchamy, H. N. Rajabi, R. Thimmapaya, A. Navaraj, and B. Thimmapaya Repression of c-Myc and inhibition of G1 exit in cells conditionally overexpressing p300 that is not dependent on its histone acetyltransferase activity PNAS, August 5, 2003; 100(16): 9524 - 9529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Braastad, Z. Han, and E. A. Hendrickson Constitutive DNase I Hypersensitivity of p53-Regulated Promoters J. Biol. Chem., February 28, 2003; 278(10): 8261 - 8268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wu and D. M. Terrian Regulation of Caveolin-1 Expression and Secretion by a Protein Kinase Cepsilon Signaling Pathway in Human Prostate Cancer Cells J. Biol. Chem., October 18, 2002; 277(43): 40449 - 40455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. McGuffie and C. V. Catapano Design of a novel triple helix-forming oligodeoxyribonucleotide directed to the major promoter of the c-myc gene Nucleic Acids Res., June 15, 2002; 30(12): 2701 - 2709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Weinmann, S. M. Bartley, T. Zhang, M. Q. Zhang, and P. J. Farnham Use of Chromatin Immunoprecipitation To Clone Novel E2F Target Promoters Mol. Cell. Biol., October 15, 2001; 21(20): 6820 - 6832. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
