Ordered changes in histone modifications at the core of the Arabidopsis circadian clock

Ordered changes in histone modifications at the core of the Arabidopsis circadian clock
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DOI:
10.1073/pnas.1217022110
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发表时间:
2012-12-26
影响因子:
11.1
通讯作者:
Mas, Paloma
Mas, Paloma
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Malapeira, Jordi;Crhak Khaitova, Lucie;Mas, Paloma

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拟南芥的生物钟功能依赖于一个复杂的振荡器组件之间的相互调节网络。在这里,我们证明,染色质重塑是一个普遍的调节机制的核心时钟。峰谷昼夜节律振荡被H3乙酰化(H3 K56 ac,K9 ac)、H3 K4三甲基化(H3 K4 me 3)和H3 K4 me 2的顺序积累所抑制。乙酰化和H3 K4 me 3的抑制废除振荡基因的表达,表明这两个标志是必不可少的基因激活。从机制上讲,阻断H3 K4 me 3导致增加的时钟阻遏物结合,表明H3 K4 me 3作为一个过渡标记调节从激活到阻遏的进展。组蛋白甲基转移酶SET DOMAIN GROUP 2/ARABIDOPSIS TRITHORAX RELATED 3(SDG 2/ATXR 3)可能直接或间接地促进这种调节,因为在错误表达SDG 2/ATXR 3的植物中,振荡基因表达、H3 K4 me 3积累和阻遏物结合被改变。尽管振荡器组件的分歧,染色质依赖的时钟基因激活机制似乎是共同的植物和哺乳动物的昼夜节律系统。
Circadian clock function in Arabidopsis thaliana relies on a complex network of reciprocal regulations among oscillator components. Here, we demonstrate that chromatin remodeling is a prevalent regulatory mechanism at the core of the clock. The peak-to-trough circadian oscillation is paralleled by the sequential accumulation of H3 acetylation (H3K56ac, K9ac), H3K4 trimethylation (H3K4me3), and H3K4me2. Inhibition of acetylation and H3K4me3 abolishes oscillator gene expression, indicating that both marks are essential for gene activation. Mechanistically, blocking H3K4me3 leads to increased clock-repressor binding, suggesting that H3K4me3 functions as a transition mark modulating the progression from activation to repression. The histone methyltransferase SET DOMAIN GROUP 2/ARABIDOPSIS TRITHORAX RELATED 3 (SDG2/ATXR3) might contribute directly or indirectly to this regulation because oscillator gene expression, H3K4me3 accumulation, and repressor binding are altered in plants misexpressing SDG2/ATXR3. Despite divergences in oscillator components, a chromatin-dependent mechanism of clock gene activation appears to be common to both plant and mammal circadian systems.