LC-MS/MS-based quantitative study of the acyl group- and site-selectivity of human sirtuins to acylated nucleosomes

Kana Tanabe, Jiaan Liu, Daiki Kato, Hitoshi Kurumizaka, Kenzo Yamatsugu, Motomu Kanai, Shigehiro A. Kawashima

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    Chromatin structure and gene expression are dynamically regulated by posttranslational modifications of histones. Recent advance in mass spectrometry has identified novel types of lysine acylations, such as butyrylation and malonylation, whose functions and regulations are likely different from those of acetylation. Sirtuins, nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, catalyze various deacylations. However, it is poorly understood how distinct sirtuins regulate the histone acylation states of nucleosomes that have many lysine residues. Here, we provide mass spectrometry-based quantitative information about the acyl group- and site-selectivity of all human sirtuins on acylated nucleosomes. The acyl group- and site-selectivity of each sirtuin is unique to its subtype. Sirt5 exclusively removes negatively-charged acyl groups, while Sirt1/2/3/6/7 preferentially remove hydrophobic acyl groups; Sirt1 and Sirt3 selectively remove acetyl group more than butyryl group, whereas Sirt2 and Sirt6 showed the opposite selectivity. Investigating site-selectivity for active sirtuins revealed acylated lysines on H4 tails to be poor substrates and acylated H3K18 to be a good substrate. Furthermore, we found Sirt7 to be a robust deacylase of H3K36/37, and its activity reliant on nucleosome-binding at its C-terminal basic region. All together, our quantitative dataset provides a useful resource in understanding chromatin regulations by histone acylations.

    元の言語English
    記事番号2656
    ジャーナルScientific Reports
    8
    発行部数1
    DOI
    出版物ステータスPublished - 2018 12 1

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    Tanabe, K., Liu, J., Kato, D., Kurumizaka, H., Yamatsugu, K., Kanai, M., & Kawashima, S. A. (2018). LC-MS/MS-based quantitative study of the acyl group- and site-selectivity of human sirtuins to acylated nucleosomes. Scientific Reports, 8(1), [2656]. https://doi.org/10.1038/s41598-018-21060-2