Lysine 2-hydroxyisobutyrylation is a novel widely distributed active histone mark Lunzhi Dai, Chao Peng, Emilie Montellier, Zhike Lu, Yue Chen, Haruhiko Ishii, Alexandra Debernardi, Thierry Buchou, Sophie Rousseaux, Fulai Jin, Benjamin R. Sabari, Zhiyou Deng, C. David Allis, Bing Ren, Saadi Khochbin, Yingming Zhao Here we report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and 63 human and mouse histone Khib sites, including 27 unique Khib sites without reported lysine acetylation (Kac) and lysine crotonylation (Kcr). This histone mark was initially identified by mass spectrometry (MS) and then exhaustively validated by both chemical and biochemical methods. Histone Khib shows distinct genomic distributions from histone Kac or histone Kcr during male germ cell differentiation. Using ChIP-seq, gene expression analysis and immunodetection, we show that in male germ cells, H4K8hib is associated with active gene transcription, in meiotic and post-meiotic cells. In addition, H4K8ac associated genes are included in and constitute only a sub-fraction of H4K8hib labeled genes. The histone Khib mark is conserved and widely distributed, has high stoichiometry, and induces a large structural change. These findings suggest its critical role on the regulation of chromatin functions. |
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