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真核生物中逆转录病毒和转座元件的整合位点选择。

Integration site selection by retroviruses and transposable elements in eukaryotes.

机构信息

Université Côte d'Azur, INSERM, CNRS, IRCAN, 28 Ave de Valombrose, 06107 Nice Cedex 02, France.

Sorbonne Paris Cité, Université Paris Diderot, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7212, Institut Universitaire d'Hématologie, Hôpital St. Louis, 1 Ave Claude Vellefaux, 75010 Paris, France.

出版信息

Nat Rev Genet. 2017 May;18(5):292-308. doi: 10.1038/nrg.2017.7. Epub 2017 Mar 13.

Abstract

Transposable elements and retroviruses are found in most genomes, can be pathogenic and are widely used as gene-delivery and functional genomics tools. Exploring whether these genetic elements target specific genomic sites for integration and how this preference is achieved is crucial to our understanding of genome evolution, somatic genome plasticity in cancer and ageing, host-parasite interactions and genome engineering applications. High-throughput profiling of integration sites by next-generation sequencing, combined with large-scale genomic data mining and cellular or biochemical approaches, has revealed that the insertions are usually non-random. The DNA sequence, chromatin and nuclear context, and cellular proteins cooperate in guiding integration in eukaryotic genomes, leading to a remarkable diversity of insertion site distribution and evolutionary strategies.

摘要

转座元件和逆转录病毒存在于大多数基因组中,它们可能具有致病性,并且被广泛用作基因传递和功能基因组学工具。探索这些遗传元件是否针对特定的基因组位点进行整合,以及这种偏好是如何实现的,对于我们理解基因组进化、癌症和衰老中的体细胞基因组可塑性、宿主-寄生虫相互作用以及基因组工程应用至关重要。通过下一代测序对整合位点进行高通量分析,结合大规模基因组数据挖掘和细胞或生化方法,揭示了插入通常是非随机的。在真核基因组中,DNA 序列、染色质和核环境以及细胞蛋白协同作用,指导整合,导致插入位点分布和进化策略的显著多样性。

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