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人类和啮齿动物中L1的表达与调控。

L1 expression and regulation in humans and rodents.

作者信息

Rosser James M, An Wenfeng

机构信息

School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA.

出版信息

Front Biosci (Elite Ed). 2012 Jan 1;4(6):2203-25. doi: 10.2741/537.

Abstract

Long interspersed elements type 1 (LINE-1s, or L1s) have impacted mammalian genomes at multiple levels. L1 transcription is mainly controlled by its 5' untranslated region (5'UTR), which differs significantly among active human and rodent L1 families. In this review, L1 expression and its regulation are examined in the context of human and rodent development. First, endogenous L1 expression patterns in three different species-human, rat, and mouse-are compared and contrasted. A detailed account of relevant experimental evidence is presented according to the source material, such as cell lines, tumors, and normal somatic and germline tissues from different developmental stages. Second, factors involved in the regulation of L1 expression at both transcriptional and posttranscriptional levels are discussed. These include transcription factors, DNA methylation, PIWI-interacting RNAs (piRNAs), RNA interference (RNAi), and posttranscriptional host factors. Similarities and differences between human and rodent L1s are highlighted. Third, recent findings from transgenic mouse models of L1 are summarized and contrasted with those from endogenous L1 studies. Finally, the challenges and opportunities for L1 mouse models are discussed.

摘要

长散在核元件1型(LINE-1s,或L1s)在多个层面影响了哺乳动物基因组。L1转录主要受其5'非翻译区(5'UTR)控制,活跃的人类和啮齿动物L1家族的该区域存在显著差异。在这篇综述中,我们在人类和啮齿动物发育的背景下研究了L1的表达及其调控。首先,比较并对比了人类、大鼠和小鼠这三种不同物种的内源性L1表达模式。根据细胞系、肿瘤以及来自不同发育阶段的正常体细胞和生殖细胞组织等来源材料,详细介绍了相关实验证据。其次,讨论了在转录和转录后水平上参与L1表达调控的因素。这些因素包括转录因子、DNA甲基化、PIWI相互作用RNA(piRNAs)、RNA干扰(RNAi)以及转录后宿主因子。突出了人类和啮齿动物L1之间的异同。第三,总结了L1转基因小鼠模型的最新研究结果,并与内源性L1研究结果进行了对比。最后,讨论了L1小鼠模型面临的挑战和机遇。

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