Conte Caroline, Dastugue Bernard, Vaury Chantal
Unité INSERM 384, Faculté de Médecine, 28 place Henri-Dunant, 63000 Clermont-Ferrand, France.
EMBO J. 2002 Jul 15;21(14):3908-16. doi: 10.1093/emboj/cdf367.
Enhancers can function over great distances and interact with almost any kind of promoter, but insulators or promoter competition generally limit their effect to a single gene. We provide in vivo evidence that retroelements may establish promoter competition with their neighboring genes and restrict the range of action of an enhancer. We report that the retroelement Idefix from Drosophila melanogaster inhibits white gene expression in testes by a promoter competition mechanism that does not occur in the eyes. The sequence specificity of the two TATA-less promoters of white and Idefix is a prime determinant in the competition that takes place in tissues where both are transcriptionally active. This study brings to light a novel mechanism whereby transcriptional interference by an active retrotransposon may perturb expression of neighboring genes. This capacity to interfere with the transcriptional regulation of their host, together with the facts that retroelements preferentially move within the germline and do not excise to replicate, suggest that these elements are cis-regulatory sequences able to imprint specific and heritable controls essential for eukaryotic gene regulation.
增强子可以在远距离发挥作用,并与几乎任何类型的启动子相互作用,但绝缘子或启动子竞争通常将它们的作用限制在单个基因上。我们提供了体内证据,表明反转录元件可能与其相邻基因建立启动子竞争,并限制增强子的作用范围。我们报告说,果蝇的反转录元件Idefix通过一种在眼睛中不发生的启动子竞争机制抑制睾丸中的白色基因表达。白色基因和Idefix的两个无TATA框启动子的序列特异性是在两者都具有转录活性的组织中发生的竞争的主要决定因素。这项研究揭示了一种新机制,即活跃的反转录转座子的转录干扰可能会扰乱相邻基因的表达。这种干扰宿主转录调控的能力,以及反转录元件优先在种系内移动且不切除以进行复制的事实,表明这些元件是能够印记对真核基因调控至关重要的特定和可遗传控制的顺式调控序列。