Displacement of an E-Box-Binding Repressor by Basic HelixLoop-Helix Proteins: Implications for B-Cell Specificity of the Immunoglobulin Heavy-Chain Enhancer

作者：Tom Genetta, Diane M. Ruezinsky, Tom R. Kadesch · 发表于：Molecular and Cellular Biology · 年份：1994 · DOI：10.1128/mcb.14.9.6153-6163.1994 · 被引用次数：168 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、NF-κB Signaling Pathways

The activity of the immunoglobulin heavy-chain (IgH) enhancer is restricted to B cells, although it binds both B-cell-restricted and ubiquitous transcription factors. Activation of the enhancer in non-B cells upon overexpression of the basic helix-loop-helix (bHLH) protein E2A appears to be mediated not only by the binding of E2A to its cognate E box but also by the resulting displacement of a repressor from that same site. We have identified a "two-handed" zinc finger protein, denoted ZEB, the DNA-binding specificity of which mimics that of the cellular repressor. By employing a derivative E box that binds ZEB but not E2A, 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 proteins. Hence, we propose that a necessary prerequisite of enhancer activity is the B-cell-specific displacement of a ZEB-like repressor by bHLH proteins.