Age-associated de-repression of retrotransposons in the Drosophila fat body, its potential cause and consequence.
Age-associated de-repression of retrotransposons in the Drosophila fat body, its potential cause and consequence.
复制标题
DOI：
10.1111/acel.12465
复制
发表时间：
2016-06
期刊：
影响因子：
7.8
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Chen H;Zheng X;Xiao D;Zheng Y
真核基因组含有转座因子（TE），激活后可以移动到新的位置。由于TE（包括逆转录转座子和DNA转座子）的不受控制的转座可导致DNA断裂和基因组不稳定性，因此包括异染色质介导的抑制在内的多种机制已发展为抑制TE活化。对模式生物的研究表明，由于异染色质的年龄相关失调，TE在衰老时被激活。考虑到不同的生物体或细胞类型在衰老时可能经历不同的异染色质变化，重要的是要确定导致特定组织和细胞类型中TE激活的途径。通过对分离的RNA进行深度测序，我们报告了在旧的果蝇脂肪体中许多逆转录转座子的表达增加，该脂肪体是一种相当于哺乳动物肝脏和脂肪组织的器官。这种去抑制与衰老脂肪体细胞中DNA损伤灶数量增加和果蝇核纤层蛋白B水平降低相关。果蝇核纤层蛋白B在幼仔或幼虫脂肪体中的缺失导致异染色质的减少以及反转录转座子表达和DNA损伤的相应增加。核纤层蛋白B和反转录转座子表达的进一步操作表明核纤层蛋白通过抑制反转录转座子在维持果蝇脂肪体基因组完整性中的作用。
Eukaryotic genomes contain transposable elements (TE) that can move into new locations upon activation. Since uncontrolled transposition of TEs, including the retrotransposons and DNA transposons, can lead to DNA breaks and genomic instability, multiple mechanisms, including heterochromatin‐mediated repression, have evolved to repress TE activation. Studies in model organisms have shown that TEs become activated upon aging as a result of age‐associated deregulation of heterochromatin. Considering that different organisms or cell types may undergo distinct heterochromatin changes upon aging, it is important to identify pathways that lead to TE activation in specific tissues and cell types. Through deep sequencing of isolated RNAs, we report an increased expression of many retrotransposons in the old Drosophila fat body, an organ equivalent to the mammalian liver and adipose tissue. This de‐repression correlates with an increased number of DNA damage foci and decreased level of Drosophila lamin‐B in the old fat body cells. Depletion of the Drosophila lamin‐B in the young or larval fat body results in a reduction of heterochromatin and a corresponding increase in retrotransposon expression and DNA damage. Further manipulations of lamin‐B and retrotransposon expression suggest a role of the nuclear lamina in maintaining the genome integrity of the Drosophila fat body by repressing retrotransposons.