Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark
Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark
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DOI：
10.1038/nchembio.1497
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发表时间：
2014-05-01
影响因子：
14.8
通讯作者：
Zhao, Yingming
中科院分区：
文献类型：
--
作者：
Dai, Lunzhi;Peng, Chao;Zhao, Yingming
我们报道了一种新型组蛋白标记——赖氨酸2 - 羟基异丁酰化（K - hib）的鉴定，并在63个人类和小鼠组蛋白Khib位点确定了该标记，其中包括27个独特的赖氨酸位点，这些位点此前未知会被赖氨酸乙酰化（K - ac）和赖氨酸巴豆酰化（K - cr）修饰。这种组蛋白标记最初通过质谱法鉴定，随后通过化学和生化方法进行了验证。在雄性生殖细胞分化过程中，组蛋白Khib呈现出与组蛋白Kac或组蛋白Kcr不同的基因组分布。通过染色质免疫沉淀测序、基因表达分析和免疫检测，我们发现，在雄性生殖细胞中，H4K8（hib）与减数分裂和减数分裂后细胞中的活性基因转录相关。此外，与H4K8（ac）相关的基因包含在H4K8hib标记的基因中，且仅构成其一个亚组。组蛋白Khib标记是保守的且广泛分布，具有较高的化学计量比，并能引起较大的结构变化。这些发现表明它在染色质功能调控中起着关键作用。
We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (K-hib), 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 (K-ac) and lysine crotonylation (K-cr). 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, H4K8(hib) is associated with active gene transcription in meiotic and post-meiotic cells. In addition, H4K8(ac)-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.