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Nat Chem Biol. 2014 May;10(5):365-70. doi: 10.1038/nchembio.1497. Epub 2014 Mar 30.

Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark.

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Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
INSERM, U823, Université Joseph Fourier-Grenoble 1, Institut Albert Bonniot, Faculté de Médecine, La Tronche, France.
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California-San Diego School of Medicine, La Jolla, California, USA.
Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.


We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse histone Khib sites, including 27 unique lysine sites that are not known to be modified by lysine acetylation (Kac) and lysine crotonylation (Kcr). This histone mark was initially identified by MS and then validated by chemical and biochemical methods. Histone Khib shows distinct genomic distributions from histone Kac or histone Kcr during male germ cell differentiation. Using chromatin immunoprecipitation sequencing, 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 subfraction 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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