Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus:: Analysis at c-fos and c-jun
Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus:: Analysis at c-fos and c-jun
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DOI：
10.1371/journal.pbio.0030393
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发表时间：
2005-12-01
期刊：
影响因子：
9.8
通讯作者：
Mahadevan, LC
中科院分区：
文献类型：
--
作者：
Hazzalin, CA;Mahadevan, LC
目前基因诱导研究的一个主要焦点涉及染色质和核小体调控，特别是在这一过程中多种组蛋白修饰如磷酸化、乙酰化和甲基化的意义。我们在小鼠细胞核中发现了所有赖氨酸4 （K4）甲基化组蛋白H3的一个新的生理特征，区别于赖氨酸9甲基化组蛋白H3。k4甲基化的组蛋白H3受到持续动态乙酰化的影响，而赖氨酸9甲基化的H3则不会。我们之前报道过动态组蛋白H3磷酸化和乙酰化是可诱导原癌基因c-fos和c-jun的关键特征。我们在这里表明，这些基因上动态乙酰化的组蛋白H3也被k4甲基化。虽然这三种修饰被证明在这些基因的同一核小体上共存，但在基因诱导过程中，磷酸化和乙酰化会短暂出现，而在整个过程中，K4甲基化仍然可以检测到。最后，我们讨论了组蛋白乙酰化翻转在基因诱导过程中的功能意义。我们发现，尽管在这些基因上引起组蛋白乙酰化增强，但对周转的抑制会立即抑制基因诱导。这些数据表明，所有k4甲基化组蛋白H3都受到hat和hdac的持续作用，并表明在c-fos和c-jun，与主流模型相反，周转和不稳定增强的乙酰化与有效的基因诱导有关。
A major focus of current research into gene induction relates to chromatin and nucleosomal regulation, especially the significance of multiple histone modifications such as phosphorylation, acetylation, and methylation during this process. We have discovered a novel physiological characteristic of all lysine 4 (K4)-methylated histone H3 in the mouse nucleus, distinguishing it from lysine 9-methylated H3. K4-methylated histone H3 is subject to continuous dynamic turnover of acetylation, whereas lysine 9-methylated H3 is not. We have previously reported dynamic histone H3 phosphorylation and acetylation as a key characteristic of the inducible proto-oncogenes c-fos and c-jun. We show here that dynamically acetylated histone H3 at these genes is also K4-methylated. Although all three modifications are proven to co-exist on the same nucleosome at these genes, phosphorylation and acetylation appear transiently during gene induction, whereas K4 methylation remains detectable throughout this process. Finally, we address the functional significance of the turnover of histone acetylation on the process of gene induction. We find that inhibition of turnover, despite causing enhanced histone acetylation at these genes, produces immediate inhibition of gene induction. These data show that all K4-methylated histone H3 is subject to the continuous action of HATs and HDACs, and indicates that at c-fos and c-jun, contrary to the predominant model, turnover and not stably enhanced acetylation is relevant for efficient gene induction.