Active genes are tri-methylated at K4 of histone H3

Active genes are tri-methylated at K4 of histone H3
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DOI:
10.1038/nature01080
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发表时间:
2002-09-26
期刊:
影响因子:
64.8
通讯作者:
Kouzarides, T
Kouzarides, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Santos-Rosa, H;Schneider, R;Kouzarides, T

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体内组蛋白的赖氨酸甲基化发生在三种状态:单甲基、二甲基和三甲基(1)。已发现组蛋白H3在活跃的常染色质区域的赖氨酸4 (K4)处发生二甲基化,而在沉默的异染色质位点则没有(2)。本研究表明,酿酒酵母Set1蛋白可以催化K4二甲基化和三甲基化,并刺激许多基因的活性。利用区分K4二甲基化和三甲基化状态的抗体,我们发现二甲基化发生在非活性和活性的常染色质基因上,而三甲基化只存在于活性基因上。因此,三甲基化K4的存在定义了基因表达的活跃状态。这些发现建立了甲基状态作为基因活性决定因素的概念,从而大大扩展了组蛋白修饰的复杂性。
Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl(1). Histone H3 has been found to be dimethylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites(2). Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri- methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri- methylated state of K4 we show that di- methylation occurs at both inactive and active euchromatic genes, whereas tri- methylation is present exclusively at active genes. It is therefore the presence of a trimethylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.