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转座元件邻域对正常组织和肿瘤组织中人类基因表达的影响。

Influence of the transposable element neighborhood on human gene expression in normal and tumor tissues.

作者信息

Lerat Emmanuelle, Sémon Marie

机构信息

Université de Lyon, Université Lyon 1, CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, 43 boulevard du 11 novembre 1918, Villeurbanne F-69622, France.

出版信息

Gene. 2007 Jul 15;396(2):303-11. doi: 10.1016/j.gene.2007.04.002. Epub 2007 Apr 6.

DOI:10.1016/j.gene.2007.04.002
PMID:17490832
Abstract

Transposable elements (TEs) are genomic sequences able to replicate themselves, and to move from one chromosomal position to another within the genome. Many TEs contain their own regulatory regions, which means that they may influence the expression of neighboring genes. TEs may also be activated and transcribed in various cancers. We therefore tested whether gene expression in normal and tumor tissues is influenced by the neighboring TEs. To do this, we associated all human genes to the nearest TEs. We analyzed the expression of these genes in normal and tumor tissues using SAGE and EST data, and related this to the presence and type of TEs in their vicinity. We confirmed that TEs tend to be located in antisense orientation relative to their hosting genes. We found that the average number of tissues where a gene is expressed varies depending on the type of TEs located near the gene, and that the difference in expression level between normal and tumor tissues is greatest for genes that host SINE elements. This deregulation increases with the number of SINE copies in the gene vicinity. This suggests that SINE elements might contribute to the cascade of gene deregulation in cancer cells.

摘要

转座元件(TEs)是能够自我复制,并在基因组内从一个染色体位置移动到另一个位置的基因组序列。许多转座元件含有自身的调控区域,这意味着它们可能影响邻近基因的表达。转座元件在各种癌症中也可能被激活并转录。因此,我们测试了正常组织和肿瘤组织中的基因表达是否受邻近转座元件的影响。为此,我们将所有人类基因与最近的转座元件相关联。我们使用SAGE和EST数据分析了这些基因在正常组织和肿瘤组织中的表达,并将其与附近转座元件的存在和类型相关联。我们证实,转座元件相对于其宿主基因倾向于以反义方向定位。我们发现,一个基因表达的组织平均数量因位于该基因附近的转座元件类型而异,并且对于宿主为SINE元件的基因,正常组织和肿瘤组织之间的表达水平差异最大。这种失调随着基因附近SINE拷贝数的增加而增加。这表明SINE元件可能促成癌细胞中基因失调的级联反应。

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