ETS-Core Binding Factor: a Common Composite Motif in Antigen Receptor Gene Enhancers

A tripartite domain of the murine immunoglobulin μ heavy-chain enhancer contains the μA and μB elements that bind ETS proteins and the μE3 element that binds leucine zipper-containing basic helix-loop-helix (bHLH-zip) factors. Analysis of the corresponding region of the human μ enhancer revealed high conservation of the μA and μB motifs but a striking absence of the μE3 element. Instead of bHLH-zip proteins, we found that the human enhancer bound core binding factor (CBF) between the μA and μB elements; CBF binding was shown to be a common feature of both murine and human enhancers. Furthermore, mutant enhancers that bound prototypic bHLH-zip proteins but not CBF did not activate transcription in B cells, and conversely, CBF transactivated the murine enhancer in nonlymphoid cells. Taking these data together with the earlier analysis of T-cell-specific enhancers, we propose that ETS-CBF is a common composite element in the regulation of antigen receptor genes. In addition, these studies identify the first B-cell target of CBF, a protein that has been implicated in the development of childhood pre-B-cell leukemias.