Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation.
Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation.
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DOI：
10.1016/j.molcel.2009.07.017
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发表时间：
2009-09-11
期刊：
影响因子：
16
通讯作者：
Shilatifard, Ali
中科院分区：
文献类型：
--
作者：
Schulze, Julia M.;Jackson, Jessica;Nakanishi, Shima;Gardner, Jennifer M.;Hentrich, Thomas;Haug, Jeff;Johnston, Mark;Jaspersen, Sue L.;Kobor, Michael S.;Shilatifard, Ali
为了确定H3 K79甲基化Dot 1的差异模式所需的分子调节剂，我们进行了GPS筛选，发现细胞周期调节的SBF复合物的组分是正常水平的H3 K79二甲基化而不是三甲基化所需的。全基因组定位显示，H3 K79二甲基化和三甲基化在染色质上呈现相互排斥的模式，M/G1细胞周期调控基因显著富集H3 K79二甲基化。由于H3 K79三甲基化需要H2 B的预先单泛素化，我们进行了H2 BK 123单泛素化的全基因组分析，并显示H2 BK 123单泛素化被排除在细胞周期调控基因和含有H3 K79 me 2的位点之外，但不被排除在含有H3 K79 me 3的区域之外。对负责建立/去除H3 K79二甲基化的因子的全基因组筛选导致鉴定了几个基因，包括NRM 1和WHI 3，它们都影响SBF和MBF复合物的转录，进一步将H3 K79甲基化状态的调节与细胞周期联系起来。
To define the molecular regulators required for differential pattern of H3K79 methylation by Dot1, we performed a GPS screen and discovered that the components of the cell cycle-regulated SBF complex were required for normal levels of H3K79 di- but not trimethylation. Genome-wide mapping revealed that H3K79 di- and trimethylation to present a mutually exclusive pattern on chromatin with M/G1 cell-cycle-regulated genes significantly enriched for H3K79 dimethylation. Since H3K79 trimethylation requires prior monoubiquitination of H2B, we performed genome-wide profiling of H2BK123 monoubiquitination and showed that H2BK123 monoubiquitination is excluded from cell cycle regulated genes and sites containing H3K79me2 but not from H3K79me3 containing regions. A genome-wide screen for factors responsible for the establishment/removal of H3K79 dimethylation resulted in the identification of several genes including NRM1 and WHI3, which both impact the transcription by the SBF, and MBF complexes, further linking the regulation of H3K79’s methylation status to the cell cycle.
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