Acetylation is known to be one of the major post-translational modifications of histones. The acetylation level of histones is regulated by the enzymatic activities of HAT and HDAC. Dozens of structurally divergent classes of HDAC inhibitors have been identified. They have been shown to induce cell-cycle arrest, cell differentiation and apoptosis in various cancer cell lines and to inhibit tumor growth in animals or humans. Histone deacetylase inhibitors elevate the acetylation level by blocking or reducing the deacetylation activities of HDACs reacting with specific acetylated lysine residues. An analytical method which can ascertain the acetylation or lack of acetylation at a given lysine residue in a histone is needed to provide detailed information on the effect of treatment with a HDAC inhibitor drug. Recently, specific post-translational modification sites on histones have been identified and studied in detail by mass spectrometry. In this review, we will summarize the mass spectrometric methods to identify histone acetylation sites and quantify the acetylation level. These methods are applied to the evaluation of the efficacy of histone deacetylase inhibitor drugs through modulation of histone acetylation.
Keywords: Chromosomal RNA, chromatin transcriptional factors, histone deactylases (HDAC), isoleucine, Tandem Mass Spectrometry, Protein-Sequencing, electron capture dissociation (ECD)
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