Histone deacetylase inhibitors globally enhance h3/h4 tail acetylation without affecting h3 lysine 56 acetylation.
Histone deacetylase inhibitors globally enhance h3/h4 tail acetylation without affecting h3 lysine 56 acetylation.
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DOI：
10.1038/srep00220
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发表时间：
2012
影响因子：
4.6
通讯作者：
Thibault P
中科院分区：
文献类型：
--
作者：
Drogaris P;Villeneuve V;Pomiès C;Lee EH;Bourdeau V;Bonneil E;Ferbeyre G;Verreault A;Thibault P
组蛋白去乙酰化酶抑制剂（HDACi）代表了用于癌症治疗的有希望的途径。我们应用质谱法（MS）来确定临床相关HDACi对组蛋白乙酰化的总体水平的影响。完整的组蛋白分析显示，HDACi SAHA和MS-275在正常二倍体成纤维细胞和转化的人细胞中全面增加组蛋白H3和H4乙酰化。组蛋白H3赖氨酸56乙酰化（H3 K56 ac）最近引起了很大的兴趣和争议，由于其作为诊断和预后标志物的广泛多样性的癌症的潜力。使用定量MS，我们证明了H3 K56 ac比以前报道的人细胞中的丰度低得多。出乎意料的是，与H3/H4 N-末端尾部乙酰化相反，H3 K56 ac响应于每类HDAC的抑制剂没有增加。此外，我们证明了针对H3 K56 ac肽产生的抗体与H3 N-末端尾部乙酰化位点交叉反应，该位点与H3 K56侧翼残基具有序列相似性。
Histone deacetylase inhibitors (HDACi) represent a promising avenue for cancer therapy. We applied mass spectrometry (MS) to determine the impact of clinically relevant HDACi on global levels of histone acetylation. Intact histone profiling revealed that the HDACi SAHA and MS-275 globally increased histone H3 and H4 acetylation in both normal diploid fibroblasts and transformed human cells. Histone H3 lysine 56 acetylation (H3K56ac) recently elicited much interest and controversy due to its potential as a diagnostic and prognostic marker for a broad diversity of cancers. Using quantitative MS, we demonstrate that H3K56ac is much less abundant than previously reported in human cells. Unexpectedly, in contrast to H3/H4 N-terminal tail acetylation, H3K56ac did not increase in response to inhibitors of each class of HDACs. In addition, we demonstrate that antibodies raised against H3K56ac peptides cross-react against H3 N-terminal tail acetylation sites that carry sequence similarity to residues flanking H3K56.