Cloning and transcription factor-binding sites of the human c- rel proto-oncogene promoter

Abstract

We report here the cloning, sequencing, functional analysis and DNase I footprinting of the human c- rel promoter region. The results revealed an 824-bp BsaAI-StuI minimal promoter region with a large number of NF-κB, Ap2 and Spl-binding sites, some of them variants of known consensus sequences. This is the first promoter in the Rel/NF-κB/IκB family to be subjected to a detailed footprinting analysis for the binding of transcription activator proteins. Our finding of 14 Ap2-binding sites may indicate why the human c- rel promoter, unlike the chicken c- rel promoter, has a strong function and is highly responsive to phorbol esters. The presence of five NF-κB and six Spl-binding sites in turn adds to growing evidence that, in mammals, the promoter of the Rel/NF-κB/IκB family may utilize multiple NF-κB- and Spl-binding sites for their interactive regulation. Furthermore, there are putative binding sites for the PU.1 and Oct 1 2 transcription activator proteins, also present in the mouse c- rel promoter, which may help explain the preferential transcription of the c- rel gene in B- and T-lymphoid cells.