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鱼类特异性转座元件塑造了斑马鱼中 p53 靶基因的库。

A fish-specific transposable element shapes the repertoire of p53 target genes in zebrafish.

机构信息

Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

出版信息

PLoS One. 2012;7(10):e46642. doi: 10.1371/journal.pone.0046642. Epub 2012 Oct 31.

Abstract

Transposable elements, as major components of most eukaryotic organisms' genomes, define their structural organization and plasticity. They supply host genomes with functional elements, for example, binding sites of the pleiotropic master transcription factor p53 were identified in LINE1, Alu and LTR repeats in the human genome. Similarly, in this report we reveal the role of zebrafish (Danio rerio) EnSpmN6_DR non-autonomous DNA transposon in shaping the repertoire of the p53 target genes. The multiple copies of EnSpmN6_DR and their embedded p53 responsive elements drive in several instances p53-dependent transcriptional modulation of the adjacent gene, whose human orthologs were frequently previously annotated as p53 targets. These transposons define predominantly a set of target genes whose human orthologs contribute to neuronal morphogenesis, axonogenesis, synaptic transmission and the regulation of programmed cell death. Consistent with these biological functions the orthologs of the EnSpmN6_DR-colonized loci are enriched for genes expressed in the amygdala, the hippocampus and the brain cortex. Our data pinpoint a remarkable example of convergent evolution: the exaptation of lineage-specific transposons to shape p53-regulated neuronal morphogenesis-related pathways in both a hominid and a teleost fish.

摘要

转座元件作为大多数真核生物基因组的主要组成部分,定义了它们的结构组织和可塑性。它们为宿主基因组提供了功能性元件,例如,在人类基因组中的 LINE1、Alu 和 LTR 重复序列中鉴定出了多效性主转录因子 p53 的结合位点。同样,在本报告中,我们揭示了斑马鱼(Danio rerio)EnSpmN6_DR 非自主 DNA 转座子在塑造 p53 靶基因库中的作用。EnSpmN6_DR 的多个拷贝及其嵌入的 p53 反应元件在多个实例中驱动邻近基因的 p53 依赖性转录调节,其人类同源物先前经常被注释为 p53 靶标。这些转座子主要定义了一组靶基因,其人类同源物有助于神经元形态发生、轴突发生、突触传递和程序性细胞死亡的调节。与这些生物学功能一致,EnSpmN6_DR 定殖基因座的同源物富含在杏仁核、海马体和大脑皮层中表达的基因。我们的数据指出了一个显著的趋同进化的例子:谱系特异性转座子的适应进化,以塑造同源人和硬骨鱼中的 p53 调节的神经元形态发生相关途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/249f/3485254/c53ecf279e3d/pone.0046642.g001.jpg

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