Trichostatin A down-regulate DNA methyltransferase 1 in Jurkat T cells
Trichostatin A down-regulate DNA methyltransferase 1 in Jurkat T cells
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DOI：
10.1016/j.canlet.2006.03.010
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发表时间：
2007-02-08
期刊：
影响因子：
9.7
通讯作者：
Jagodzinski, Pawel P.
中科院分区：
文献类型：
--
作者：
Januchowski, Radoslaw;Dabrowski, Mikolaj;Jagodzinski, Pawel P.
组蛋白去乙酰酶抑制剂曲古抑素A(TSA)单独能够激活DNA甲基化介导的沉默基因在人类癌细胞中的转录。在结肠癌、肺癌、肝癌、前列腺癌和乳腺癌中发现DNA甲基转移酶DNMT1的表达和半衰期增加。通过实时定量聚合酶链式反应和Western印迹分析，我们发现TSA下调了Jurkat T白血病细胞克隆E6-1中DNMT1的mRNA和蛋白表达。我们还观察到TSA降低了DNMT1mRNA的稳定性，并将其半衰期从大约7小时缩短到2小时。我们还发现，DNMT1 mRNA的转录后调节需要蛋白质的生物合成，这表明RNase和/或mRNA稳定蛋白实体参与了DNMT1转录的稳定。我们的研究结果表明，TSA不仅改变了组蛋白的乙酰化，还可能影响DNA甲基化。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
Histone deacetylase inhibitor Trichostatin A (TSA), alone, is able to activate the transcription of DNA methylation-mediated silenced genes in human cancer cells. Increase in expression and half-life of the DNA methyltransferase DNMT1 has been found in carcinomas of the colon, lung, liver, prostate, and breast cancer. This overexpression of DNMT1 is responsible for hypermethylation of regulatory sequences of many genes involved in tumorigenesis.Using quantitative real-time PCR and Western blot analysis, we found that TSA down-regulate DNMT1 mRNA and protein expression in Jurkat T leukemia cells clone E6-1. We also observed that TSA decreased DNMT1 mRNA stability and reduced this transcript half-life from approximately 7 to 2 h. We also found that protein biosynthesis is needed for posuranscriptional regulation of DNMT1 mRNA, which suggests the involvement of an RNase and/or mRNA stabilization protein entity in DNMT1 transcript stabilization.Our findings suggest that TSA not only alters histone acetylation, but also may affect DNA methylation. (c) 2006 Elsevier Ireland Ltd. All rights reserved.