(Some) cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1.
(Some) cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1.
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DOI：
10.1371/journal.pone.0053895
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nexø BA
中科院分区：
文献类型：
--
作者：
Laska MJ;Nissen KK;Nexø BA
DNA甲基化和组蛋白乙酰化是表观遗传修饰，其作为基因表达的调节剂。DNA甲基化被认为是哺乳动物基因组中逆转录元件沉默的重要机制。然而，人类内源性逆转录病毒（HERVs）的甲基化还没有得到很好的研究。本研究的目的是更详细地研究HERV-Fc 1前病毒5′LTR的转录潜力，并在许多细胞系中检测CpG甲基化对该LTR的特异性影响。具体而言，研究了去甲基化化学物质如5-氮杂-2 ′脱氧胞苷和曲古抑菌素-A在诱导或重新激活HERV-Fc 1特异性序列表达中的作用及其机制。在我们目前的研究中，5-aza-dC被证明是HERV-Fc 1的强大诱导剂，同时它强烈抑制DNA甲基化。用这种去甲基化剂5-aza-dC处理导致先前不表达HERV-Fc 1或表达水平非常低的细胞中HERV-Fc 1表达水平显著增加。HERV-Fc 1 RNA的表达程度与相关DNA序列的脱甲基化程度精确相关。总之，结果表明，DNA甲基化/组蛋白脱乙酰酶的抑制可以干扰影响人类细胞中HERV-Fc 1表达的基因沉默机制。
DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs) is not well investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5′LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2′ deoxycytidine and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza-dC, results in significantly increased levels of HERV-Fc1 expression in cells previously not expressing HERV-Fc1, or with a very low expression level. The extent of expression of HERV-Fc1 RNAs precisely correlates with the apparent extent of demethylation of the related DNA sequences. In conclusion, the results suggest that inhibition of DNA methylation/histone deacetylase can interfere with gene silencing mechanisms affecting HERV-Fc1 expression in human cells.
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影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
DOI：
10.1073/pnas.78.10.6290
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
NIWA, O;SUGAHARA, T
通讯作者：
SUGAHARA, T
影响因子：
37.3
作者：
Menendez L;Benigno BB;McDonald JF
通讯作者：
McDonald JF
影响因子：
3.7
作者：
Jern, P;Sperber, GO;Blomberg, J
通讯作者：
Blomberg, J
影响因子：
6.7
作者：
Blazkova J;Trejbalova K;Gondois-Rey F;Halfon P;Philibert P;Guiguen A;Verdin E;Olive D;Van Lint C;Hejnar J;Hirsch I
通讯作者：
Hirsch I