Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, 612 65, Brno, Czech Republic.
Epigenomics. 2013 Aug;5(4):379-96. doi: 10.2217/epi.13.38.
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.
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.
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.
组蛋白乙酰化和去乙酰化之间的最佳平衡对于基因的正常功能很重要。因此，我们研究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。
通过 cDNA 微阵列和 Western blot 研究了组蛋白乙酰转移酶和/或组蛋白去乙酰化酶抑制剂处理后细胞信号通路的变化。
我们分析了组蛋白去乙酰化酶抑制剂 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 显著下调了与 DNA 修复相关的基因，包括 Rad51、Rad54 和 BRCA2。然而，MG149 除了剪接体网络和参与 DNA 修复的 Sestrins 之外，对所研究的核过程没有影响。
基于我们的结果，我们提出研究中的表观遗传药物具有根据其各自的分子靶点影响特定细胞信号通路的独特潜力。
