Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing defects in Saccharomyces cerevisiae
Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing defects in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.c500097200
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发表时间：
2005-08-05
影响因子：
4.8
通讯作者：
Briggs, SD
中科院分区：
文献类型：
--
作者：
Fingerman, IM;Wu, CL;Briggs, SD
翻译后的组蛋白修饰，如乙酰化、磷酸化、泛素化和甲基化，与基因表达的调节有关。在酿酒酵母中，Set1已被鉴定为组蛋白H3赖氨酸4 （Lys(4)）甲基化所需的唯一组蛋白甲基转移酶。不表达Set1的酵母细胞有几种明显的表型，包括生长缓慢和端粒缺陷、HML和rDNA沉默。然而，Set1甲基转移酶介导组蛋白H3差异甲基化（单-、二-和三-）的机制仍不清楚，Set1中参与H3 Lys(4)甲基化的结构域或区域尚未得到很好的表征。在这项研究中，Set1的N端被证明对全局和基因特异性组蛋白H3三甲基化很重要。我们发现Set1三甲基缺陷突变体可以挽救Set1 δ缓慢生长缺陷。相反，Set1三甲基突变体在端粒、rDNA、HML和HMR沉默方面存在缺陷。综上所述，这些数据表明组蛋白H3 Lys4三甲基化是适当沉默所必需的，而单甲基化和/或二甲基化对细胞生长是足够的。
Post-translational histone modifications, such as acetylation, phosphorylation, ubiquitination, and methylation, have been correlated with regulation of gene expression. In Saccharomyces cerevisiae, Set1 has been identified as the sole histone methyltransferase required for histone H3 lysine 4 ( Lys(4)) methylation. Yeast cells that do not express Set1 have several apparent phenotypes, including slow growth and defects in telomere, HML, and rDNA silencing. However, the mechanism by which the Set1 methyltransferase mediates differential histone H3 methylation ( mono-, di-, and tri-) is still not understood, and the involvement of domains or regions in Set1 contributing to H3 Lys(4) methylation has not been well characterized. In this study, the N terminus of Set1 was shown to be important for global and gene specific histone H3 trimethylation. We show that Set1 trimethyl-defective mutants can rescue a set1 Delta slow growth defect. In contrast, Set1 trimethyl mutants were defective in telomere, rDNA, HML, and HMR silencing. Taken together, these data suggest that histone H3 Lys4 trimethylation is required for proper silencing, while mono- and/or dimethylation is sufficient for cell growth.