Histone H3 lysine 4 methylation patterns in higher eukaryotic genes
Histone H3 lysine 4 methylation patterns in higher eukaryotic genes
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DOI：
10.1038/ncb1076
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发表时间：
2004-01-01
影响因子：
21.3
通讯作者：
Kouzarides, T
中科院分区：
文献类型：
--
作者：
Schneider, R;Bannister, AJ;Kouzarides, T
组蛋白内的赖氨酸残基可被单甲基化、二甲基化或三甲基化。在酿酒酵母中，组蛋白H3的赖氨酸4（K4/H3）的三甲基化与转录活性相关，但在高等真核生物中这种甲基化状态鲜为人知。在此，我们检测了后生动物基因启动子和转录区域的K4/H3甲基化模式。我们分析了发育受调控的、组成性活跃或不活跃的鸡基因。我们发现K4/H3甲基化模式与酿酒酵母有相似之处。三甲基K4/H3在5'转录区域达到峰值，并且活跃基因可通过与不活跃基因相比具有高水平的三甲基K4/H3加以区分。然而，我们的结果也明确了与酵母相比存在的差异，因为在β -珠蛋白基因座内的不活跃基因上存在显著水平的K4/H3甲基化，这意味着这种修饰在维持一种“预备”的染色质状态中起作用。此外，K4/H3二甲基化并非在全基因组范围内存在，并且二甲基化在整个转录区域并非均匀分布。这些结果表明，在后生动物中，K4/H3的二甲基化和三甲基化与活跃转录相关，并且与酿酒酵母相比，全基因组甲基化模式存在显著差异。
Lysine residues within histones can be mono-, di - or tri-methylated. In Saccharomyces cerevisiae tri-methylation of Lys 4 of histone H3 (K4/H3) correlates with transcriptional activity, but little is known about this methylation state in higher eukaryotes. Here, we examine the K4/H3 methylation pattern at the promoter and transcribed region of metazoan genes. We analysed chicken genes that are developmentally regulated, constitutively active or inactive. We found that the pattern of K4/H3 methylation shows similarities to S. cerevisiae. Tri-methyl K4/H3 peaks in the 5' transcribed region and active genes can be discriminated by high levels of tri-methyl K4/H3 compared with inactive genes. However, our results also identify clear differences compared to yeast, as significant levels of K4/H3 methylation are present on inactive genes within the beta-globin locus, implicating this modification in maintaining a 'poised' chromatin state. In addition, K4/H3 di-methylation is not genome-wide and di-methylation is not uniformly distributed throughout the transcribed region. These results indicate that in metazoa, di- and tri-methylation of K4/H3 is linked to active transcription and that significant differences exist in the genome-wide methylation pattern as compared with S. cerevisiae.