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一个150碱基对转录沉默子对Ig基因重排的负调控

Negative regulation of Ig gene rearrangement by a 150-bp transcriptional silencer.

作者信息

Cocea L, Dahan A, Ferradini L, Reynaud C A, Weill J C

机构信息

INSERM, Unité 373, Faculté de Médecine Necker, Paris, France.

出版信息

Eur J Immunol. 1998 Sep;28(9):2809-16. doi: 10.1002/(SICI)1521-4141(199809)28:09<2809::AID-IMMU2809>3.0.CO;2-C.

Abstract

We previously showed that the V-J intervening sequence of the chicken lambda immunoglobulin locus contains a strong silencer that acts both on transcription and rearrangement. We show here that the transcriptional silencer activity can be ascribed to a minimal 150-bp fragment. The rearrangement silencing activity was previously shown by the replacement of the V-J intervening sequence with a neutral DNA fragment that dramatically increased the rate of rearrangement of the transgene. Insertion of the minimal silencer in this neutral fragment is shown here to result in a marked decrease in rearrangement of the transgenic construct. Strikingly, deletion of 28 bp from the 150-bp fragment abolished most of the transcriptional silencing activity and had a similar effect on rearrangement. These results conclusively correlate the silencing activity on both rearrangement and transcription.

摘要

我们之前表明,鸡λ免疫球蛋白基因座的V-J间隔序列包含一个强大的沉默子,它对转录和重排均有作用。我们在此表明,转录沉默子活性可归因于一个最小的150碱基对片段。重排沉默活性先前已通过用一个中性DNA片段替换V-J间隔序列得以证明,该中性DNA片段显著提高了转基因的重排率。在此显示,将最小沉默子插入该中性片段会导致转基因构建体重排显著减少。令人惊讶的是,从150碱基对片段中缺失28碱基对消除了大部分转录沉默活性,并且对重排有类似影响。这些结果最终将重排和转录的沉默活性联系了起来。

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