rel/NF-kappa B nuclear complexes that bind kB sites in the murine c-rel promoter are required for constitutive c-rel transcription in B-cells.
The c-rel protooncogene, a member of a transcription factor family that includes NF-kappa B, 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-kappa B (kB3 site) and is sufficient for basal expression in Jurkat T-cells. In contrast, two additional NF-kappa B-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-kappa B 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 I29B cells via a mechanism independent of the NF-kappa B 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.
Grumont
R J
RJ
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Richardson
I B
IB
Gaff
C
C
Gerondakis
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001704:Biopolymers; D004926:Escherichia coli / Q000378:metabolism; D016393:Lymphoma, B-Cell; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
D001704:Biopolymers; D016328:NF-kappa B