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首页> 外文期刊>Cancer Cell >Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach.
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Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach.

机译：通过多模态方法揭示了对癌症表观基因组的化学和基因操作的基因表达的不同影响。

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摘要

We tested the hypothesis that the effects on gene expression of altered DNA methylation by 5-aza-2'-deoxycytidine (5-aza-CdR) and genetic (DNMT knockout) manipulation of DNA are similar, and distinct from Trichostatin A (TSA)-induced chromatin decondensation. Surprisingly, the effects of 5-aza-CdR were more similar to those of TSA than to DNMT1, DNMT3B, or double DNMT somatic cell knockout. Furthermore, the effects of 5-aza-CdR were similar at one and five days exposure, suggesting active demethylation or direct influence of both drugs on the stability of methylation and/or chromatin marks. Agents that induce gene activation through hypomethylation may have unintended consequences, since nearly as many genes were downregulated as upregulated after demethylation. In addition, a 75 kb cluster of metallothionein genes was coordinately regulated.
机译：我们测试了以下假设，即5-氮杂-2'-脱氧胞苷（5-氮杂-CdR）和DNA的遗传（DNMT敲除）操作对DNA甲基化改变的基因表达的影响相似，并且不同于曲古抑菌素A（TSA） -诱导的染色质缩聚。令人惊讶的是，5-氮杂-CdR的作用与TSA的作用相比，更类似于DNMT1，DNMT3B或双重DNMT体细胞敲除。此外，在暴露第1天和第5天，5-氮杂-CdR的作用相似，表明这两种药物均具有活性脱甲基作用或直接影响甲基化和/或染色质标记的稳定性。通过脱甲基作用诱导基因激活的试剂可能会产生意想不到的后果，因为脱甲基后几乎有许多基因被下调与上调。另外，对金属硫蛋白基因的75kb簇进行了协调调节。

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