DISPLACEMENT OF AN E-BOX-BINDING REPRESSOR BY BASIC HELIX-LOOP-HELIX PROTEINS - IMPLICATIONS FOR B-CELL SPECIFICITY OF THE IMMUNOGLOBULIN HEAVY-CHAIN ENHANCER
DISPLACEMENT OF AN E-BOX-BINDING REPRESSOR BY BASIC HELIX-LOOP-HELIX PROTEINS - IMPLICATIONS FOR B-CELL SPECIFICITY OF THE IMMUNOGLOBULIN HEAVY-CHAIN ENHANCER
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DOI：
10.1128/mcb.14.9.6153
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发表时间：
1994-09-01
影响因子：
5.3
通讯作者：
KADESCH, T
中科院分区：
文献类型：
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作者：
GENETTA, T;RUEZINSKY, D;KADESCH, T
免疫球蛋白重链（IgH）增强子的活性仅限于B细胞，尽管它结合B细胞限制性转录因子和普遍存在的转录因子。碱性螺旋-环-螺旋（bHLH）蛋白E2 A过表达时，非B细胞中增强子的激活似乎不仅由E2 A与其同源E盒的结合介导，而且还由来自同一位点的阻遏物的置换介导。我们已经鉴定了一种“双手”锌指蛋白，称为ZEB，其DNA结合特异性模拟细胞阻遏物的DNA结合特异性。通过使用结合ZEB而不结合E2 A的衍生E盒，我们已经表明阻遏物在B细胞中是有活性的，并且IgH增强子在没有bHLH蛋白的结合竞争的情况下被沉默。因此，我们提出增强子活性的必要前提是BHLH蛋白对ZEB样阻遏物的B细胞特异性置换。
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.