Promoter crosstalk effects on gene expression

Promoter crosstalk effects on gene expression
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DOI:
10.1016/j.jmb.2006.10.009
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发表时间:
2007-01-26
影响因子:
5.6
通讯作者:
Gossen, Manfred
Gossen, Manfred
中科院分区:
生物学2区
文献类型:
--
作者:
Hampf, Mathias;Gossen, Manfred

文献摘要

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正式分配给不同的相邻基因的紧密间隔的转录信号可以在其真实的基因组背景以及工程化的转基因星座中功能性地相互作用。为了定量和定性地描述这些启动子串扰效应,我们使用了顺式连接的诱导型和组成型表达信号的各种组合。我们的结果表明,这种相互作用可以是双向的,因此很难明确地将特定启动子元件专门分配给特定基因。我们表明,特别是对于诱导型启动子,串扰效应可能会导致近端基因表达的严重扭曲,从而挑战了生成转基因动物模型和组织培养系统的既定策略。此外,这些发现为转基因转录单元的设计提供了指导,虽然这些转录单元难以与其染色体环境相互作用,但邻近基因的表达程序基本上不受影响。 (c) 2006 Elsevier Ltd. 保留所有权利。
Closely spaced transcription signals formally assigned to different, neighboring genes can functionally interact both in their authentic genomic context as well as in engineered transgene constellations. To describe these Promoter crosstalk effects quantitatively and qualitatively, we used various combinations of inducible and constitutive expression signals linked in cis. Our results demonstrate that such interactions can be bidirectional, making it difficult to unambiguously assign a particular promoter element exclusively to a specific gene. We show that especially for inducible promoters, crosstalk effects can cause a substantial distortion in the expression of proximal genes, challenging established strategies in generating transgenic animal models and tissue culture systems. Furthermore, these findings provide guidelines for the design of transgenic transcription units that, while refractory to interactions with their chromosomal environment, leave the expression programs of neighboring genes largely untouched. (c) 2006 Elsevier Ltd. All rights reserved.