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应激诱导的成年小鼠LINE-1转座子的应变及脑区特异性激活

Stress-induced strain and brain region-specific activation of LINE-1 transposons in adult mice.

作者信息

Cappucci Ugo, Torromino Giulia, Casale Assunta Maria, Camon Jeremy, Capitano Fabrizio, Berloco Maria, Mele Andrea, Pimpinelli Sergio, Rinaldi Arianna, Piacentini Lucia

机构信息

a Department of Biology and Biotechnology "C. Darwin" , Sapienza University of Rome , Rome , Italy.

b Istituto Pasteur Italia , Fondazione Cenci-Bolognetti , Rome , Italy.

出版信息

Stress. 2018 Nov;21(6):575-579. doi: 10.1080/10253890.2018.1485647. Epub 2018 Jul 11.

DOI:10.1080/10253890.2018.1485647
PMID:29996702
Abstract

Transposable elements (TEs) are conserved mobile genetic elements that are highly abundant in most eukaryotic genomes. Although the exact function of TEs is still largely unknown, it is increasingly clear that they are significantly modulated in response to stress in a wide range of organisms, either directly or indirectly through regulation of epigenetic silencing. We investigated the effect of repeated restraint stress (2 h a day, for 5 d) on transcription levels of LINE-1 (L1) retrotransposon in the brain of inbred BALB/c, DBA/2, C57BL/6N, and outbred CD1 mice. Repeated restraint stress induced strain and brain region-specific modulation of L1 activity. We observed a significant derepression of L1 transcription in the hippocampus (HIPP) of BALB/c mice and a significant downregulation in the hippocampus of C57BL/6N mice. No significant change in L1 expression was found in the other strains and brain regions. These findings indicate in mice the control of transposons expression as an additional mechanism in stress-induced pathophysiological responses, demonstrating that their regulation is highly dependent on the strain genetic background and the brain region. Lay summary Hippocampal expression of the transposon L1 is significantly altered by repeated restraint stress in mice. L1 modulation is not only region specific, but also strain dependent, suggesting that the genetic background is an important determinant of L1 response to environmental stimuli.

摘要

转座元件(TEs)是保守的可移动遗传元件,在大多数真核生物基因组中高度丰富。尽管TEs的确切功能在很大程度上仍不清楚,但越来越明显的是,它们在多种生物体中会直接或通过表观遗传沉默的调节间接响应应激而受到显著调控。我们研究了重复束缚应激(每天2小时,持续5天)对近交系BALB/c、DBA/2、C57BL/6N以及远交系CD1小鼠大脑中LINE-1(L1)逆转座子转录水平的影响。重复束缚应激诱导了L1活性的品系和脑区特异性调节。我们观察到BALB/c小鼠海马体(HIPP)中L1转录显著去抑制,而C57BL/6N小鼠海马体中L1转录显著下调。在其他品系和脑区未发现L1表达有显著变化。这些发现表明,在小鼠中,转座子表达的调控是应激诱导的病理生理反应中的一种额外机制,证明其调控高度依赖于品系遗传背景和脑区。简易总结小鼠海马体中转座子L1的表达因重复束缚应激而显著改变。L1的调节不仅具有区域特异性,还依赖于品系,这表明遗传背景是L1对环境刺激反应的重要决定因素。

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