Microarray analysis reveals global modulation of endogenous retroelement transcription by microbes.
Microarray analysis reveals global modulation of endogenous retroelement transcription by microbes.
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DOI：
10.1186/1742-4690-11-59
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发表时间：
2014-07-25
期刊：
影响因子：
3.3
通讯作者：
Kassiotis G
中科院分区：
文献类型：
--
作者：
Young GR;Mavrommatis B;Kassiotis G
小鼠和人类基因组的很大一部分由内源逆转录元件（RE）组成，其中包括内源逆转录病毒。随着进化时间的推移，RE 会积累失活突变或缺失，从而失去复制能力。此外，RE 可以通过宿主的专用机制进行转录抑制。尽管如此，它们中的许多仍然拥有并表达完整的开放阅读框，并且它们的转录活性与宿主的许多生理和病理过程相关。然而，由于对 RE 转录调控机制的了解不完全，这种关联仍然很脆弱。在这里，我们使用生物信息学工具来检查小鼠和人类免疫细胞对微生物刺激做出反应的 RE 转录活性，通过微阵列测量。体外微生物信号激活的免疫细胞不仅导致参与免疫反应的宿主基因的转录发生广泛变化，而且还导致许多 RE 的转录发生广泛变化。调节的 RE 经常被发现靠近或嵌入类似调节的宿主基因中。重点关注报告单整合、基因间 RE 的探针，揭示了这些元件对微生物信号的广泛转录反应。微生物刺激以细胞固有的方式调节 RE 表达。与这些结果一致，在小鼠和人类中，许多 RE 的转录活性根据暴露于环境微生物而遵循不同组织的特征，并且在病毒感染或肠道微生物群失衡期间进一步发生严重改变。总之，这些结果凸显了改进的方法在评估存档和新的微阵列数据集中 RE 转录谱的效用。更重要的是，这种方法的应用表明，由于病原体感染或共生微生物失调而导致的免疫激活会导致 RE 转录的全局调节。因此，RE 转录与疾病之间的任何关联都应考虑 RE 对外部刺激的反应。本文的在线版本 (doi:10.1186/1742-4690-11-59) 包含补充材料，可供授权用户使用。
A substantial proportion of both the mouse and human genomes comprise of endogenous retroelements (REs), which include endogenous retroviruses. Over evolutionary time, REs accumulate inactivating mutations or deletions and thus lose the ability to replicate. Additionally, REs can be transcriptionally repressed by dedicated mechanisms of the host. Nevertheless, many of them still possess and express intact open reading frames, and their transcriptional activity has been associated with many physiological and pathological processes of the host. However, this association remains tenuous due to incomplete understanding of the mechanism by which RE transcription is regulated. Here, we use a bioinformatics tool to examine RE transcriptional activity, measured by microarrays, in murine and human immune cells responding to microbial stimulation. Immune cell activation by microbial signals in vitro caused extensive changes in the transcription not only of the host genes involved in the immune response, but also of numerous REs. Modulated REs were frequently found near or embedded within similarly-modulated host genes. Focusing on probes reporting single-integration, intergenic REs, revealed extensive transcriptional responsiveness of these elements to microbial signals. Microbial stimulation modulated RE expression in a cell-intrinsic manner. In line with these results, the transcriptional activity of numerous REs followed characteristics in different tissues according to exposure to environmental microbes and was further heavily altered during viral infection or imbalances with intestinal microbiota, both in mice and humans. Together, these results highlight the utility of improved methodologies in assessing RE transcription profiles in both archived and new microarray data sets. More importantly, application of this methodology suggests that immune activation, as a result of infection with pathogens or dysbiosis with commensal microbes, causes global modulation of RE transcription. RE responsiveness to external stimuli should, therefore, be considered in any association between RE transcription and disease. The online version of this article (doi:10.1186/1742-4690-11-59) contains supplementary material, which is available to authorized users.
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影响因子：
1.7
作者：
Jurka, J;Kapitonov, VV;Walichiewicz, J
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影响因子：
12.3
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Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
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64.8
作者：
Best, S;LeTissier, P;Stoye, JP
通讯作者：
Stoye, JP
影响因子：
1.8
作者：
de Leeuw, Wim C;Rauwerda, Han;Jonker, Martijs J;Breit, Timo M
通讯作者：
Breit, Timo M
DOI：
10.1126/science.1221789
发表时间：
2012-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iliev ID;Funari VA;Taylor KD;Nguyen Q;Reyes CN;Strom SP;Brown J;Becker CA;Fleshner PR;Dubinsky M;Rotter JI;Wang HL;McGovern DP;Brown GD;Underhill DM
通讯作者：
Underhill DM