Ingvarsdottir Kristin, Edwards Chris, Lee Min Gyu, Lee Jung Shin, Schultz David C, Shilatifard Ali, Shiekhattar Ramin, Berger Shelley L
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Mol Cell Biol. 2007 Nov;27(22):7856-64. doi: 10.1128/MCB.00801-07. Epub 2007 Sep 17.
In mammalian cells, histone lysine demethylation is carried out by two classes of enzymes, the LSD1/BHC110 class and the jumonji class. The enzymes of the jumonji class in the yeast Saccharomyces cerevisiae have recently also been shown to have lysine demethylation activity. Here we report that the protein encoded by YJR119c (termed KDM5), coding for one of five predicted jumonji domain proteins in yeast, specifically demethylates trimethylated histone H3 lysine 4 (H3K4me3), H3K4me2, and H3K4me1 in vitro. We found that loss of KDM5 increased mono-, di-, and trimethylation of lysine 4 during activation of the GAL1 gene. Interestingly, cells deleted of KDM5 also displayed a delayed reduction of K4me3 upon reestablishment of GAL1 repression. These results indicate that K4 demethylation has two roles at GAL1, first to establish appropriate levels of K4 methylation during gene activation and second to remove K4 trimethylation during the attenuation phase of transcription. Thus, analysis of lysine demethylation in yeast provides new insight into the physiological roles of jumonji demethylase enzymes.
在哺乳动物细胞中，组蛋白赖氨酸去甲基化由两类酶催化，即LSD1/BHC110类和Jumonji类。最近研究发现，酿酒酵母中的Jumonji类酶也具有赖氨酸去甲基化活性。本文报道，酵母中预测的五个含Jumonji结构域蛋白之一YJR119c编码的蛋白（称为KDM5），在体外可特异性地使三甲基化组蛋白H3赖氨酸4（H3K4me3）、H3K4me2和H3K4me1去甲基化。我们发现，在GAL1基因激活过程中，KDM5缺失会增加赖氨酸4的单甲基化、二甲基化和三甲基化。有趣的是，缺失KDM5的细胞在重新建立GAL1基因抑制时，K4me3的减少也会延迟。这些结果表明，K4去甲基化在GAL1基因处有两个作用，一是在基因激活过程中建立适当水平的K4甲基化，二是在转录衰减阶段去除K4三甲基化。因此，对酵母中赖氨酸去甲基化的分析为Jumonji去甲基化酶的生理作用提供了新的见解。
