School of Biological Sciences, Seoul National University, Seoul, 151-747, Korea.
Mol Cells. 2012 Sep;34(3):279-87. doi: 10.1007/s10059-012-0103-5. Epub 2012 Aug 8.
Circadian clock genes are regulated by a transcriptional-translational feedback loop. In Arabidopsis, LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) transcripts are highly expressed in the morning. Translated LHY and CCA1 proteins repress the expression of TIMING OF CAB EXPRESSION 1 (TOC1), which peaks in the evening. TOC1 protein induces expression of LHY and CCA1, forming a negative feedback loop which is believed to constitute the oscillatory mechanism of the clock. The rhythmic oscillation of mouse clock genes mPERIOD 1 (mPER1) and mPER2 has been correlated with regular alteration of chromatin structure through histone acetylation/deacetylation. However, little is known about the relationship between the transcriptional activity of Arabidopsis clock genes and their chromatin status. Here, we report that histone H3 acetylation (H3Ac) and H3 lysine 4 tri-methylation (H3K4me3) levels at LHY, CCA1, and TOC1 are positively correlated with the rhythmic transcript levels of these genes, whereas H3K36me2 level shows a negative correlation. Thus, our study suggests rhythmic transcription of Arabidopsis clock genes might be regulated by rhythmic histone modification, and it provides a platform for future identification of clock-controlling histone modifiers.
生物钟基因受转录-翻译反馈回路调控。在拟南芥中,LATE ELONGATED HYPOCOTYL(LHY)和 CIRCADIAN CLOCK ASSOCIATED 1(CCA1)转录本在早上高度表达。翻译的 LHY 和 CCA1 蛋白抑制 TIMING OF CAB EXPRESSION 1(TOC1)的表达,TOC1 蛋白在晚上达到峰值。TOC1 蛋白诱导 LHY 和 CCA1 的表达,形成一个负反馈环,被认为是时钟的振荡机制。小鼠生物钟基因 mPERIOD 1(mPER1)和 mPER2 的节律性振荡与通过组蛋白乙酰化/去乙酰化的染色质结构的规律性改变有关。然而,关于拟南芥生物钟基因的转录活性与其染色质状态之间的关系知之甚少。在这里,我们报告说,LHY、CCA1 和 TOC1 处的组蛋白 H3 乙酰化(H3Ac)和 H3 赖氨酸 4 三甲基化(H3K4me3)水平与这些基因的节律性转录水平呈正相关,而 H3K36me2 水平呈负相关。因此,我们的研究表明,拟南芥生物钟基因的节律性转录可能受节律性组蛋白修饰调控,并为未来鉴定时钟控制组蛋白修饰剂提供了一个平台。