ETS-core binding factor: a common composite motif in antigen receptor gene enhancers

A tripartite domain of the murine immunoglobulin mu heavy-chain enhancer contains the mu A and mu B elements that bind ETS proteins and the mu E3 element that binds leucine zipper containing basic helix-loop helix (bHLH-zip) factors, Analysis of the corresponding region of the human mu enhancer revealed high conservation of the mu A and mu B motifs but a striking absence of the mu E3 element, Instead of bHLH-zip proteins, we found that the human enhancer bound core binding factor (CBF) between the mu A and mu B elements; CBF binding mas shown to be a common feature of both murine and human enhancers, Furthermore, mutant enhancers that hound 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,vith 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.