E2F mediates induction of the Sp1-controlled promoter of the human DNA polymerase epsilon B-subunit gene POLE2

The B-subunits of replicative DNA polymerases from Archaea to humans belong to the same protein family, suggesting that they share a common fundamenta l function, We report here the gene structure for the B-subunit of human DN A polymerase epsilon (POLE2), whose expression and transcriptional regulati on is typical for replication proteins with some unique features. The 75 bp core promoter region, located within exon 1, contains an Spl element that is a critical determinant of promoter activity as shown by the luciferase r eporter, electrophoretic mobility shift and DNase footprinting assays. Two overlapping E2F elements adjacent to the Spl element are essential for full promoter activity and serum response, Binding sites for E2F1 and NF-1 resi de immediately downstream from the core promoter region, Our results sugges t that human POLE2 is regulated by two E2F-pocket protein complexes, one as sociated with Spl and the other with NF-1, So far, only one replicative DNA polymerase B-subunit gene promoter, POLA2 encoding the B-subunit of DNA po lymerase alpha, has been characterized. Mitogenic activation of the POLE2 p romoter by an E2F-mediated mechanism resembles that of POLA2, but the regul ation of basal promoter activity is different between these two genes.