Basic nuclear processes affected by histone acetyltransferases and histone deacetylase inhibitors
Basic nuclear processes affected by histone acetyltransferases and histone deacetylase inhibitors
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DOI：
10.2217/epi.13.38
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发表时间：
2013-08-01
期刊：
影响因子：
3.8
通讯作者：
Bartova, Eva
中科院分区：
文献类型：
--
作者：
Legartova, Sona;Stixova, Lenka;Bartova, Eva
目的：组蛋白乙酰化和脱乙酰化之间的最佳平衡对于基因的正常功能非常重要。因此，我们探讨了组蛋白修饰酶抑制剂如何调节核事件，包括复制、转录、剪接和 DNA 修复。材料和方法：通过 cDNA 微阵列和蛋白质印迹研究用组蛋白乙酰转移酶和/或组蛋白脱乙酰酶抑制剂处理后细胞信号传导途径的变化。结果：我们分析了组蛋白脱乙酰酶抑制剂辛二酰苯胺异羟肟酸 (SAHA) 和组蛋白乙酰酶抑制剂 MG149 的作用。 SAHA 改变了参与 DNA 复制复合物、基础转录和剪接体途径的因子的表达。 SAHA 显着下调了 DNA 修复相关基因，包括 Rad51、Rad54 和 BRCA2。然而，除了参与 DNA 修复的剪接体网络和 Sestrins 之外，MG149 对所研究的核过程没有影响。结论：根据我们的结果，我们提出所研究的表观遗传药物根据其各自的分子靶标具有影响特定细胞信号传导途径的独特潜力。
Aim: The optimal balance between histone acetylation and deacetylation is important for proper gene function. Therefore, we addressed how inhibitors of histone-modifying enzymes can modulate nuclear events, including replication, transcription, splicing and DNA repair. Materials & methods: Changes in cell signaling pathways upon treatment with histone acetyltransferases and/or histone deacetylase inhibitors were studied by cDNA microarrays and western blots. Results: We analyzed the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and the histone acetylase inhibitor MG149. SAHA altered the expression of factors involved in DNA replication complexes, basal transcription and the spliceosome pathway. DNA repair-related genes, including Rad51, Rad54 and BRCA2, were significantly downregulated by SAHA. However, MG149 had no effect on the investigated nuclear processes, with the exception of the spliceosome network and Sestrins, involved in DNA repair. Conclusion: Based on our results, we propose that the studied epigenetic drugs have the distinct potential to affect specific cell signaling pathways depending on their respective molecular targets.