Comparative methylation of ERVWE1/syncytin-1 and other human endogenous retrovirus LTRs in placenta tissues.

Comparative methylation of ERVWE1/syncytin-1 and other human endogenous retrovirus LTRs in placenta tissues.
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DOI:
10.1093/dnares/dsp011
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发表时间:
2009-08
期刊:
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子:
--
通讯作者:
Mallet F
Mallet F
中科院分区:
其他
文献类型:
--
作者:
Gimenez J;Montgiraud C;Oriol G;Pichon JP;Ruel K;Tsatsaris V;Gerbaud P;Frendo JL;Evain-Brion D;Mallet F

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人内源性逆转录病毒(HERVs)在体细胞中是全局沉默的。然而,一些HERV在生理条件下显示高转录。特别是,ERVWE 1、ERVFRDE 1和ERV 3(不同家族的三种前病毒)在胎盘中高度转录,并产生与胎盘发育相关的包膜蛋白。由于重复元件的沉默被认为主要通过DNA甲基化发生,我们比较了ERVWE 1和相关HERV的甲基化,以了解HERV甲基化是否依赖于家族、整合位点、组织、长末端重复序列(LTR)功能或相关基因功能。胎盘相关组织中HERV-W LTR的CpG甲基化是异质性的,但发现ERVWE 1 5′LTR及其并列增强子(哺乳动物表观LTR反转录转座子)的联合表观遗传控制。此外,ERVWE 1、ERVFRDE 1和ERV 3 5′ LTR在妊娠期间的细胞滋养层细胞中基本上都是低甲基化的,但表现出不同的阶段依赖性甲基化特征。在非细胞滋养层细胞中,它们也表现出不同的甲基化谱,与它们各自的转录活性相一致。细胞系中转录活性和LTR甲基化的比较分析进一步支持了甲基化在控制功能性LTR中的作用。这些结果表明HERV甲基化可能不是家族相关的,而是拷贝特异性的,并且与LTR功能和组织相关。特别是,ERVWE 1和ERV 3可能是发育表观遗传调控的HERV。
Human endogenous retroviruses (HERVs) are globally silent in somatic cells. However, some HERVs display high transcription in physiological conditions. In particular, ERVWE1, ERVFRDE1 and ERV3, three proviruses of distinct families, are highly transcribed in placenta and produce envelope proteins associated with placenta development. As silencing of repeated elements is thought to occur mainly by DNA methylation, we compared the methylation of ERVWE1 and related HERVs to appreciate whether HERV methylation relies upon the family, the integration site, the tissue, the long terminal repeat (LTR) function or the associated gene function. CpG methylation of HERV-W LTRs in placenta-associated tissues was heterogeneous but a joint epigenetic control was found for ERVWE1 5′LTR and its juxtaposed enhancer, a mammalian apparent LTR retrotransposon. Additionally, ERVWE1, ERVFRDE1 and ERV3 5′LTRs were all essentially hypomethylated in cytotrophoblasts during pregnancy, but showed distinct and stage-dependent methylation profiles. In non-cytotrophoblastic cells, they also exhibited different methylation profiles, compatible with their respective transcriptional activities. Comparative analyses of transcriptional activity and LTR methylation in cell lines further sustained a role for methylation in the control of functional LTRs. These results suggest that HERV methylation might not be family related but copy-specific, and related to the LTR function and the tissue. In particular, ERVWE1 and ERV3 could be developmentally epigenetically regulated HERVs.
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