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首页> 外文期刊>The Journal of investigative dermatology. >Promoter-Specific Hypomethylation Is Associated with Overexpression of PLS3, GATA6, and TWIST1 in the Sezary Syndrome
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Promoter-Specific Hypomethylation Is Associated with Overexpression of PLS3, GATA6, and TWIST1 in the Sezary Syndrome

机译：启动子特异的次甲基化与Sezary综合征中PLS3，GATA6和TWIST1的过表达有关

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摘要

The Sezary Syndrome (SS) is an aggressive CD4+ leukemic variant of cutaneous T-cell lymphoma. Epigenetic modification of cancer cell genome is often linked to the expression of important cancer-related genes. Here we addressed the hypothesis that, in SS, DNA hypomethylation is involved in upregulation of PLS3, GATA6, and TWIST1, genes that are undetected in normal lymphocytes. Pyrosequencing analysis of CpG rich regions, and CpG dinucleatides within the 5' regulatory regions, confirmed hypomethylation of all three genes in SS, compared with controls. We then studied how methylation regulates PLS3 transcription in vitro using PLS3-negative (Jurkat) and PLS3-positive (HT-1080) cell lines. Treatment with the hypomethylating agent 5-azacytidine induced PLS3 expression in Jurkat cells and in vitro methylation of the cloned PLS3 promoter suppressed luciferase expression in HT-1080 cells. In conclusion, we show that promoter hypomethylation is associated with PLS3, GATA6, and TWIST1 overexpression in SS CD4+ T cells and that methylation can regulate PLS3 expression in vitro. The mechanisms of DNA hypomethylation in vivo and the functional role of PLS3, TWIST1, and GATA6 in SS are being investigated.
机译：Sezary综合征（SS）是皮肤T细胞淋巴瘤的侵袭性CD4 +白血病变体。癌细胞基因组的表观遗传修饰通常与重要的癌症相关基因的表达有关。在这里，我们解决了以下假设：在SS中，DNA低甲基化与PLS3，GATA6和TWIST1的上调有关，而在正常淋巴细胞中未检测到这些基因。与对照相比，对富含CpG的区域和5'调控区内的CpG二核苷酸进行焦磷酸测序分析，证实了SS中所有三个基因的甲基化不足。然后，我们研究了甲基化如何使用PLS3阴性（Jurkat）和PLS3阳性（HT-1080）细胞系体外调节PLS3转录。用次甲基化剂5-氮杂胞苷处理可诱导Jurkat细胞中PLS3表达，而克隆的PLS3启动子的体外甲基化可抑制HT-1080细胞中的荧光素酶表达。总之，我们表明启动子低甲基化与SS CD4 + T细胞中的PLS3，GATA6和TWIST1过表达有关，并且甲基化可以调节体外的PLS3表达。正在研究体内DNA低甲基化的机制以及PLS3，TWIST1和GATA6在SS中的功能。

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