Zhang Kai, Li Liyan, Zhu Mengxiao, Wang Guojuan, Xie Jianjun, Zhao Yunlong, Fan Enguo, Xu Liyan, Li Enmin
Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou 515041, China; State Key Laboratory of Medicinal Chemical Biology, Department of Chemistry, Nankai University, Tianjin 300071, China.
Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China.
J Proteomics. 2015 Jan 1;112:180-9. doi: 10.1016/j.jprot.2014.09.004. Epub 2014 Sep 16.
Eukaryotic DNA is packaged into a chromatin with the help of four core histones (H2A, H2B, H3, and H4). Diverse histone post-translational modifications (PTMs) are hence involved in the regulation of gene transcription. However, how this regulation does work is still poorly understood and lacks details. Here we used the mass spectrometry-based proteomics approach to perform a comparative analysis of histone marks at a global level in two phenotypes of esophageal squamous cell carcinoma (ESCC) with different invasiveness. We obtained a comprehensive profiling of histone H3 and H4 PTMs including lysine methylation, acetylation and novel butyrylation. The correlation between histone marks and cancer invasive capabilities was further characterized and one distinguishable PTM, H4K79me2 was discovered and verified in this study. Immunohistochemistry analysis suggests that abnormal level of H4K79me2 may be related to poor survival of ESCC patients. Our results enrich the dataset of the feature pattern of global histone PTMs in ESCC cell lines.
Core histone proteins, decorated by multiple biological significant protein post-translational modifications (PTMs) such as lysine acetylation and lysine methylation, are considered to regulate gene transcription and be associated with the development of cancer. Recent studies have further shown that global level of histone modifications is the potential hallmark of cancer to predict the clinical outcomes of human cancers. However, the regulation mechanism is largely unknown. Here we used the mass spectrometry based proteomics coupled with stable isotope labeling with amino acids in cell culture (SILAC) to characterize the global levels of histone marks in two phenotypes of esophageal squamous cell carcinoma (ESCC) cell lines with different invasive capabilities. To the best of our knowledge, it is the first report about the comparative analysis for histone marks of the different invasive ESCC cell lines. A significantly differential level of histone modification, H4K79me2, was determined and verified. Immunohistochemistry analysis further suggests that abnormal level of H4K79me2 may be related to poor survival of ESCC patients. Our results could contribute to understanding the different expressions of global histone PTMs in different invasive ESCC cell lines.
真核生物的DNA在四种核心组蛋白（H2A、H2B、H3和H4）的帮助下包装成染色质。因此，多种组蛋白翻译后修饰（PTM）参与基因转录的调控。然而，这种调控是如何发挥作用的仍知之甚少且缺乏细节。在这里，我们使用基于质谱的蛋白质组学方法，在两种具有不同侵袭性的食管鳞状细胞癌（ESCC）表型中，对组蛋白标记进行了全局水平的比较分析。我们获得了组蛋白H3和H4 PTM的全面图谱，包括赖氨酸甲基化、乙酰化和新发现的丁酰化。进一步表征了组蛋白标记与癌症侵袭能力之间的相关性，并在本研究中发现并验证了一种可区分的PTM，即H4K79me2。免疫组织化学分析表明，H4K79me2水平异常可能与ESCC患者的不良生存相关。我们的结果丰富了ESCC细胞系中全局组蛋白PTM特征模式的数据集。
核心组蛋白由多种具有生物学意义的蛋白质翻译后修饰（PTM）修饰，如赖氨酸乙酰化和赖氨酸甲基化，被认为可调节基因转录并与癌症的发生发展相关。最近的研究进一步表明，组蛋白修饰的全局水平是预测人类癌症临床结果的潜在癌症标志物。然而，其调控机制在很大程度上尚不清楚。在这里，我们使用基于质谱的蛋白质组学结合细胞培养中氨基酸的稳定同位素标记（SILAC），来表征两种具有不同侵袭能力的食管鳞状细胞癌（ESCC）细胞系中组蛋白标记的全局水平。据我们所知，这是关于不同侵袭性ESCC细胞系组蛋白标记比较分析的首次报道。确定并验证了一种显著差异的组蛋白修饰水平，即H4K79me2。免疫组织化学分析进一步表明，H4K79me2水平异常可能与ESCC患者的不良生存相关。我们的结果有助于理解不同侵袭性ESCC细胞系中全局组蛋白PTM的不同表达。
