The histone methyltransferase MLL1 permits the oscillation of circadian gene expression.
The histone methyltransferase MLL1 permits the oscillation of circadian gene expression.
复制标题
组蛋白甲基转移酶MLL1允许昼夜节律表达的振荡。
DOI：
10.1038/nsmb.1961
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发表时间：
2010-12
影响因子：
16.8
通讯作者：
Sassone-Corsi P
中科院分区：
文献类型：
--
作者：
Katada S;Sassone-Corsi P
分子钟的经典观点是基于互锁的转录-翻译反馈环。由于哺乳动物基因组的很大一部分是以昼夜节律的方式表达的，染色质重塑已被提出在时钟功能中起关键作用。在这里，我们表明，组蛋白H3的K4三甲基化是有节奏的，并遵循与先前描述的H3 K9/K14乙酰化昼夜节律启动子相同的配置文件。MLL 1是三胸果蝇（Drosophila trithorax）的哺乳动物同源物，是参与转录控制的H3 K4特异性甲基转移酶。我们证明了MLL 1对于昼夜节律转录和循环H3 K4三甲基化是必不可少的。MLL 1与CLOCK：BMAL 1形成复合物，并有助于它们有节奏地募集到昼夜节律启动子和H3乙酰化。值得注意的是，MLL 1未能与CLOCKΔ19相互作用，这为这种突变的显性负功能提供了解释。我们的研究结果有利于这样一种情况，即MLL 1组蛋白甲基转移酶的H3 K4三甲基化需要建立一个昼夜节律转录的染色质允许状态。
The classical view of the molecular clock is based on interlocked transcriptional-translational feedback loops. Since a substantial fraction of the mammalian genome is expressed in a circadian manner, chromatin remodelling has been proposed to play a critical role in clock function. Here, we show that K4 tri-methylation of histone H3 is rhythmic and follows the same profile as previously described H3K9/K14 acetylation on circadian promoters. MLL1, a mammalian homologue of Drosophila trithorax, is a H3K4 specific methyltransferase implicated in transcriptional control. We demonstrate that MLL1 is essential for circadian transcription and cyclic H3K4 tri-methylation. MLL1 is in a complex with CLOCK:BMAL1 and contributes to their rhythmic recruitment to circadian promoters and to H3 acetylation. Remarkably, MLL1 fails to interact with CLOCKΔ19, providing an explanation for this mutations dominant negative function. Our results favor a scenario in which H3K4 tri-methylation by the MLL1 histone methyltrasferase are required to establish a chromatin permissive state for circadian transcription.
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影响因子：
9.2
作者：
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通讯作者：
Kyriacou, CP
影响因子：
8.8
作者：
Canaani, E;Nakamura, T;Rozovskaia, T;Smith, S T;Mori, T;Croce, C M;Mazo, A
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通讯作者：
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作者：
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作者：
Belden, William J.;Loros, Jennifer J.;Dunlap, Jay C.
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Dunlap, Jay C.