Genic and global functions for Paf1C in chromatin modification and gene expression in Arabidopsis.
Genic and global functions for Paf1C in chromatin modification and gene expression in Arabidopsis.
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DOI：
10.1371/journal.pgen.1000077
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发表时间：
2008-08-22
期刊：
影响因子：
4.5
通讯作者：
van Nocker S
中科院分区：
文献类型：
--
作者：
Oh S;Park S;van Nocker S
在芽殖酵母中，基因内组蛋白修饰通过保守的调节因子Paf1C与转录延伸相关联。为了研究Paf1C在高等真核生物中的相关功能，我们分析了Paf1C缺失对组蛋白H3密度和拟南芥基因中K4、K27和K36处H3甲基化模式的影响，并将其与现有的基因表达数据相结合。Paf1C的缺失并没有改变染色质中H3K4me3或H3K36me2的总体丰度，而是导致基因中H3K4me3分布的3 ′移位和H3K36me2分布的5 ′移位。我们发现植物Paf1C调控的基因对H3K4me3和H3K27me3都表现出强烈的富集，并且还表现出高度的组织特异性表达。在Paf1C和PcG调控的基因FLC，转录沉默和损失的H3K4me3和H3K36me2伴随着扩展的H3K27me3到启动子和转录起始区域和进一步富集的H3K27me3的转录区域内。这些结果突出了植物Paf1C在组蛋白修饰和基因表达中的基因和全局功能，并将转录活性与细胞记忆联系起来。在真核生物中，DNA与组蛋白和其他蛋白质一起包装成一种称为染色质的动态结构。组蛋白的特殊修饰--包括关键赖氨酸残基的甲基化--提供了与DNA密码协同作用的遗传信息。在酵母中，保守的转录调节因子Paf1C是通过赖氨酸-4的甲基化（一种被认为促进基因活性的修饰）来标记活性基因内的组蛋白H3所必需的。在高等真核生物中，这种机制是通过Polycomb-Group（PcG）来阐述的，PcG通过细胞分裂维持转录抑制，并涉及H3的赖氨酸-27的甲基化。在这项研究中，我们绘制了这些和其他关键的H3修改整个基因组的植物拟南芥和评估的影响，损失的Paf1C对这些修改和基因表达。我们发现Paf 1C在全球范围内发挥作用以维持基因内的组蛋白修饰，但仅是少数基因的适当表达所需的。这些通常在赖氨酸-4和赖氨酸-27甲基化中表现出高度的发育调节。在Paf1C和PcG靶向的开花调节因子FLC中，激活（赖氨酸-4）甲基化的丧失伴随着抑制性（赖氨酸-27）甲基化的进一步积累。这些结果提供了转录活性和细胞记忆之间的联系。
In budding yeast, intragenic histone modification is linked with transcriptional elongation through the conserved regulator Paf1C. To investigate Paf1C-related function in higher eukaryotes, we analyzed the effects of loss of Paf1C on histone H3 density and patterns of H3 methylated at K4, K27, and K36 in Arabidopsis genes, and integrated this with existing gene expression data. Loss of Paf1C did not change global abundance of H3K4me3 or H3K36me2 within chromatin, but instead led to a 3′ shift in the distribution of H3K4me3 and a 5′ shift in the distribution of H3K36me2 within genes. We found that genes regulated by plant Paf1C showed strong enrichment for both H3K4me3 and H3K27me3 and also showed a high degree of tissue-specific expression. At the Paf1C- and PcG-regulated gene FLC, transcriptional silencing and loss of H3K4me3 and H3K36me2 were accompanied by expansion of H3K27me3 into the promoter and transcriptional start regions and further enrichment of H3K27me3 within the transcribed region. These results highlight both genic and global functions for plant Paf1C in histone modification and gene expression, and link transcriptional activity with cellular memory. In eukaryotes, DNA is packaged with histones and other proteins into a dynamic fabric called chromatin. Specific modifications of histones—including methylation of key lysine residues—provide genetic information that acts synergistically with the DNA code. In yeast, the conserved transcriptional regulator Paf1C is required for marking histone H3 within active genes by methylation of Lysine-4, a modification thought to promote gene activity. In higher eukaryotes, this mechanism is elaborated through Polycomb-Group (PcG), which maintains transcriptional repression through cell divisions and involves methylation of Lysine-27 of H3. In this study, we mapped these and other key H3 modifications throughout the genome of the plant Arabidopsis thaliana and evaluated the effects of loss of Paf1C on these modifications and gene expression. We found that Paf1C acts globally to maintain histone modification within genes, but is required for appropriate expression of only a handful of genes. These typically showed a high degree of developmental regulation in both Lysine-4 and Lysine-27 methylation. At the flowering regulator FLC, targeted by both Paf1C and PcG, loss of activating (Lysine-4) methylation was accompanied by further accumulation of repressive (Lysine-27) methylation. These results provide a link between transcriptional activity and cellular memory.
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