Effects of Histone Deacetylase Inhibitors on Modulating H3K4 Methylation Marks - A Novel Cross-Talk Mechanism between Histone-Modifying Enzymes.
Effects of Histone Deacetylase Inhibitors on Modulating H3K4 Methylation Marks - A Novel Cross-Talk Mechanism between Histone-Modifying Enzymes.
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DOI：
10.4255/mcpharmacol.11.06
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发表时间：
2011-12
期刊：
影响因子：
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通讯作者：
Po-Hsien Huang;C. Plass;Ching S. Chen
中科院分区：
文献类型：
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作者：
Po-Hsien Huang;C. Plass;Ching S. Chen
最近的一项研究报告，组蛋白脱乙酰酶（HDAC）抑制剂AR 42和MS- 275上调前列腺癌细胞中的H3 K4甲基化标记，导致基因的转录激活，包括与肿瘤抑制和细胞分化相关的基因（1）。有证据表明，组蛋白去乙酰化和组蛋白H3 K4甲基化之间的串扰归因于这些HDAC抑制剂通过下调Sp1表达来抑制组蛋白H3赖氨酸4去甲基化酶（H3 K4 DM）的JARID 1家族（包括RBP 2、PLU-1、SMCX和LSD 1）的能力。这证明了HDAC在调节组蛋白修饰以及活化表观遗传学沉默的基因表达中的功能作用的复杂性。同样重要的是HDAC抑制剂在转录上抑制H3 K4 DM基因表达的能力，这具有治疗意义，因为几种H3 K4 DM如LSD 1和PLU-1与许多类型的恶性肿瘤的发病机制有关。
A recent study reports that histone deacetylase (HDAC) inhibitors, AR42 and MS- 275, upregulated H3K4 methylation marks in prostate cancer cells, leading to transcriptional activation of genes including those associated with roles in tumor suppression and cell differentiation (1). Evidence suggests that the crosstalk between histone deacetylation and histone H3K4 methylation is attributable to the ability of these HDAC inhibitors to repress the JARID1 family of histone H3 lysine 4 demethylases (H3K4DMs), including RBP2, PLU-1, SMCX, and LSD1, through the downregulation of Sp1 expression. This demonstrates the complexity of the functional roles of HDACs in the regulation of histone modifications as well as the activation of epigenetically silenced gene expression. Equally important is the ability of HDAC inhibitors to transcriptionally suppress H3K4DM gene expression which has therapeutic implications, in that several H3K4DMs such as LSD1 and PLU-1 have been implicated in the pathogenesis of many types of malignancies.