REGULATION OF THE DBP PROMOTER BY PAR PROTEINS AND IN LEUKEMIC-CELLS BEARING AN E2A HLF TRANSLOCATION/

The D-site binding protein (DBP) is a member of the PAR domain subfami ly of b/ZIP proteins, whose expression in the liver is highly sensitiv e to the growth state of that organ. This paper examines the regulatio n of the DBP promoter by C/EBP alpha and examines the role of autoregu lation id its expression, Of four previously characterized proximal pr omoter sites, sites I and III are shown to bind C/EBP alpha, but cotra nsfection in Hep G2 cells of a C/EBP alpha expression vector is unable to transactivate the promoter. In contrast, the expression of DBP, pa rticularly in conjunction with the related protein HLF, is able to dra matically upregulate expression directed by the proximal promoter. Del etion analysis and the use of single site reporter constructs demonstr ate that sites II and IV are highly responsive to transactivation by D BP and HLF. The DBP promoter is active in the UOC-B1 cell line, which bears a 17:19 translocation resulting in the creation of an E2A:HLF fu sion protein. The proteins binding to site IV are elevated in this lin e, suggesting that upregulation of DBP expression in response to inapp ropriate HLF activity may be mediated through this site. (C) 1998 Acad emic Press.