Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Int J Mol Sci. 2019 Nov 27;20(23):5977. doi: 10.3390/ijms20235977.
Retrotransposons can alter the regulation of genes both transcriptionally and post-transcriptionally, through mechanisms such as binding transcription factors and alternative splicing of transcripts. SINE-VNTR-Alu (SVA) retrotransposons are the most recently evolved class of retrotransposable elements, found solely in primates, including humans. SVAs are preferentially found at genic, high GC loci, and have been termed "mobile CpG islands". We hypothesise that the ability of SVAs to mobilise, and their non-random distribution across the genome, may result in differential regulation of certain pathways. We analysed SVA distribution patterns across the human reference genome and identified over-representation of SVAs at zinc finger gene clusters. Zinc finger proteins are able to bind to and repress SVA function through transcriptional and epigenetic mechanisms, and the interplay between SVAs and zinc fingers has been proposed as a major feature of genome evolution. We describe observations relating to the clustering patterns of both reference SVAs and polymorphic SVA insertions at zinc finger gene loci, suggesting that the evolution of this network may be ongoing in humans. Further, we propose a mechanism to direct future research and validation efforts, in which the interplay between zinc fingers and their epigenetic modulation of SVAs may regulate a network of zinc finger genes, with the potential for wider transcriptional consequences.
逆转录转座子可以通过结合转录因子和转录本的选择性剪接等机制，在转录和转录后水平上改变基因的调控。SINE-VNTR-Alu（SVA）逆转录转座子是最近进化的逆转座元件类群，仅存在于灵长类动物，包括人类中。SVAs 优先存在于基因、高 GC 位点，被称为“可移动的 CpG 岛”。我们假设 SVA 能够移动的能力及其在基因组中的非随机分布，可能导致某些途径的差异调控。我们分析了人类参考基因组中 SVA 的分布模式，并发现 SVA 在锌指基因簇中过度表达。锌指蛋白能够通过转录和表观遗传机制结合并抑制 SVA 的功能，SVA 和锌指之间的相互作用被认为是基因组进化的主要特征。我们描述了与锌指基因座上参考 SVA 和多态性 SVA 插入的聚类模式相关的观察结果，表明该网络的进化可能正在人类中进行。此外，我们提出了一种指导未来研究和验证工作的机制，其中锌指及其对 SVA 的表观遗传调节之间的相互作用可能调节锌指基因网络，具有更广泛的转录后果的潜力。
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