REL/NF-KB NUCLEAR-COMPLEXES THAT BIND KB SITES IN THE MURINE C-REL PROMOTER ARE REQUIRED FOR CONSTITUTIVE C-REL TRANSCRIPTION IN B-CELLS
Grumont, RJ; RICHARDSON, IB; GAFF, C; Gerondakis, S
CELL GROWTH & DIFFERENTIATION
The c-rel protooncogene, a member of a transcription factor family that includes NF-kappaB, displays a complex pattern of gene expression. To understand the basis of this expression, the regulatory region upstream of the murine c-rel transcription start sites has been cloned and characterized. Transcription of the murine c-rel gene initiates at multiple sites downstream of a GC-rich region conserved in the chicken c-rel promoter. This conserved region contains consensus transcription factor binding sites for SP-1 and NF-kappaB (kB3 site) and is sufficient for basal expression in Jurkat T-cells. In contrast, two additional NF-kappaB-like sites (kB1 and kB2) and an octamer consensus binding site, all located upstream of the conserved region, are required for expression of promoter-reporter gene constructs in the B-cell line I29B. NF-kappaB sites kB1 and kB3 bind p50/65 and p50 homodimers, whereas kB2 binds a distinct complex. The consensus octamer site, although only able to bind Oct1 and Oct2 with low affinity, appears to overlap with a binding site for a novel protein(s) expressed in I29B cells. Cotransfection studies show that p75-c-rel and a carboxyl-terminal truncated c-rel protein that lacks the known trans-activating domain both up-regulate the c-rel promoter in 129B cells via a mechanism independent of the NF-kappaB motifs, whereas a mutant c-rel protein lacking the DNA binding domain has no effect. Together, these findings suggest that, in this B-cell line, trans-activation of the c-rel promoter by rel proteins is via an indirect mechanism.