端粒和 HM 沉默中的 Dot1 和组蛋白 H3K79 甲基化。
Dot1 and histone H3K79 methylation in natural telomeric and HM silencing.
机构信息
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
出版信息
Mol Cell. 2011 Apr 8;42(1):118-26. doi: 10.1016/j.molcel.2011.03.006.
Abstract
The expression of genes residing near telomeres is attenuated through telomere position-effect variegation (TPEV). By using a URA3 reporter located at TEL-VII-L of Saccharomyces cerevisiae, it was proposed that the disruptor of telomeric silencing-1 (Dot1) regulates TPEV by catalyzing H3K79 methylation. URA3 reporter assays also indicated that H3K79 methylation is required for HM silencing. Surprisingly, a genome-wide expression analysis of H3K79 methylation-defective mutants identified only a few telomeric genes, such as COS12 at TEL-VII-L, to be subject to H3K79 methylation-dependent natural silencing. Consistently, loss of Dot1 did not globally alter Sir2 or Sir3 occupancy in subtelomeric regions, but only led to some telomere-specific changes. Furthermore, H3K79 methylation by Dot1 did not play a role in the maintenance of natural HML silencing. Therefore, commonly used URA3 reporter assays may not report on natural PEV, and therefore, studies concerning the epigenetic mechanism of silencing in yeast should also employ assays reporting on natural gene expression patterns.
摘要
端粒附近基因的表达通过端粒位置效应变异（TPEV）而减弱。通过使用位于酿酒酵母 TEL-VII-L 的 URA3 报告基因，有人提出，端粒沉默破坏因子 1（Dot1）通过催化 H3K79 甲基化来调节 TPEV。URA3 报告基因分析还表明，H3K79 甲基化对于 HM 沉默是必需的。令人惊讶的是，对 H3K79 甲基化缺陷突变体的全基因组表达分析仅鉴定出少数几个端粒基因，如 TEL-VII-L 处的 COS12，受到 H3K79 甲基化依赖性自然沉默的影响。一致地，Dot1 的缺失并没有全局改变亚端粒区域中 Sir2 或 Sir3 的占据，而只是导致一些端粒特异性的变化。此外，Dot1 催化的 H3K79 甲基化在维持自然 HML 沉默中不起作用。因此，常用的 URA3 报告基因分析可能无法报告自然的 PEV，因此，关于酵母中沉默的表观遗传机制的研究也应该采用报告自然基因表达模式的分析方法。
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Nucleic Acids Res. 2010 Dec;38(22):7991-8000. doi: 10.1093/nar/gkq689. Epub 2010 Aug 10.
2
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Genes Dev. 2010 Mar 15;24(6):574-89. doi: 10.1101/gad.1898410. Epub 2010 Mar 4.
3
Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation.将细胞周期与组蛋白修饰联系起来：SBF和H2B单泛素化机制以及H3K79二甲基化的细胞周期调控
Mol Cell. 2009 Sep 11;35(5):626-41. doi: 10.1016/j.molcel.2009.07.017. Epub 2009 Aug 13.
4
Histone H3 N-terminus regulates higher order structure of yeast heterochromatin.组蛋白H3的N端调控酵母异染色质的高级结构。
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13153-9. doi: 10.1073/pnas.0906866106. Epub 2009 Aug 3.
5
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7
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9
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