title: Comparative analysis of histone H3 and H4 post-translational modifications of esophageal squamous cell carcinoma with different invasive capabilities.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. Electronic address: Zhangkai@nankai.edu.cn.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China.
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Chemistry, Nankai University, Tianjin 300071, China.
authors.forename: Guojuan
authors.initials: G
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Chemistry, Nankai University, Tianjin 300071, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Enguo
authors.initials: E
authors.lastname: Fan
authors.affiliation: Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China. Electronic address: lyxu@stu.edu.cn.
authors.forename: Liyan
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Enmin
authors.initials: E
authors.lastname: Li
mesh_terms: D000107:Acetylation; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones; D009363:Neoplasm Proteins
keywords: Esophageal squamous cell carcinoma; Histone; Invasive capability; Mass spectrometry; Protein post-translational modifications (PTMs)