DISPLACEMENT OF AN E-BOX-BINDING REPRESSOR BY BASIC HELIX-LOOP-HELIX PROTEINS - IMPLICATIONS FOR B-CELL SPECIFICITY OF THE IMMUNOGLOBULIN HEAVY-CHAIN ENHANCER

The activity of the immunoglobulin heavy-chain (IgH) enhancer is restr icted to B cells, although it binds both B-cell-restricted and ubiquit ous transcription factors. Activation of the enhancer in non-B cells u pon overexpression of the basic helix-loop-helix (bHLH) protein E2A ap pears to be mediated not only by the binding of E2A to its cognate E b ox but also by the resulting displacement of a repressor from that sam e site. We have identified a ''two-handed'' zinc finger protein, denot ed ZEB, the DNA-binding specificity of which mimics that of the cellul ar repressor, By employing a derivative E box that binds ZEB but not E 2A, we have shown that the repressor is active in B cells and the IgH enhancer is silenced in the absence of binding competition by bHLH pro teins. Hence, we propose that a necessary prerequisite of enhancer act ivity is the B-cell-specific displacement of a ZEB-like repressor by b HLH proteins.