Nucleic Acids Research, 2001, Vol. 29, No. 13 2810-2821
© 2001 Oxford University Press
E2F mediates induction of the Sp1-controlled promoter of the human DNA polymerase 
B-subunit gene POLE2
1Biocenter Oulu and Department of Biochemistry, PO Box 3000, FIN-90014 University of Oulu, Finland, 2Department of Oncology, KFC, Huddinge University Hospital AB, S-14186 Stockholm, Sweden, 3Department of Medical Microbiology, PO Box 5000, FIN-90014 University of Oulu, Finland and 4Department of Biology, University of Joensuu, PO Box 111, FIN-80101 Joensuu, Finland
The B-subunits of replicative DNA polymerases from Archaea to humans belong to the same protein family, suggesting that they share a common fundamental function. We report here the gene structure for the B-subunit of human DNA polymerase 
(POLE2), whose expression and transcriptional regulation is typical for replication proteins with some unique features. The 75 bp core promoter region, located within exon 1, contains an Sp1 element that is a critical determinant of promoter activity as shown by the luciferase reporter, electrophoretic mobility shift and DNase I footprinting assays. Two overlapping E2F elements adjacent to the Sp1 element are essential for full promoter activity and serum response. Binding sites for E2F1 and NF-1 reside immediately downstream from the core promoter region. Our results suggest that human POLE2 is regulated by two E2F–pocket protein complexes, one associated with Sp1 and the other with NF-1. So far, only one replicative DNA polymerase B-subunit gene promoter, POLA2 encoding the B-subunit of DNA polymerase 
, has been characterized. Mitogenic activation of the POLE2 promoter by an E2F-mediated mechanism resembles that of POLA2, but the regulation of basal promoter activity is different between these two genes.
* To whom correspondence should be addressed at: Biocenter Oulu and Department of Biochemistry, PO Box 3000, FIN-90014 University of Oulu, Finland. Tel: +358 8 553 1155; Fax: +358 8 553 1141; Email: juhani.syvaoja{at}oulu.fi Present address: Deqi Huang, Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Elkon, C. Linhart, R. Sharan, R. Shamir, and Y. Shiloh Genome-Wide In Silico Identification of Transcriptional Regulators Controlling the Cell Cycle in Human Cells Genome Res., May 1, 2003; 13(5): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Nichols, T. Itoh, F. Zolezzi, S. Hutsell, and S. Linn Basal transcriptional regulation of human damage-specific DNA-binding protein genes DDB1 and DDB2 by Sp1, E2F, N-myc and NF1 elements Nucleic Acids Res., January 15, 2003; 31(2): 562 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Haugwitz, M. Wasner, M. Wiedmann, K. Spiesbach, K. Rother, J. Mossner, and K. Engeland A single cell cycle genes homology region (CHR) controls cell cycle-dependent transcription of the cdc25C phosphatase gene and is able to cooperate with E2F or Sp1/3 sites Nucleic Acids Res., May 1, 2002; 30(9): 1967 - 1976. [Abstract] [Full Text] [PDF]
|
|