Determinants of Histone H3K4 Methylation Patterns.
Determinants of Histone H3K4 Methylation Patterns.
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DOI：
10.1016/j.molcel.2017.10.013
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发表时间：
2017-11-16
期刊：
影响因子：
16
通讯作者：
Buratowski S
中科院分区：
文献类型：
--
作者：
Soares LM;He PC;Chun Y;Suh H;Kim T;Buratowski S
不同的因素差异识别三甲基化组蛋白H3赖氨酸4（H3 K4 me 3）附近的启动子，H3 K4 me 2下游，和启动子远端H3 K4 me 1调节基因表达。这种甲基化“梯度”被认为是H3 K4甲基转移酶Set 1/COMPASS与启动子近端RNA聚合酶II优先结合的结果。然而，其他研究表明，特定位置的线索变构激活Set 1。ChIP-Seq实验表明，活性基因上的H3 K4甲基化模式不是通用的或固定的，并且响应于转录延伸率和频率以及COMPASS活性降低而变化。将Set 1融合到RNA聚合酶II导致H3 K4 me 2遍布转录区域，并且在高度转录的基因上类似地延伸H3 K4 me 3。Tethered Set 1仍然需要组蛋白H2 B泛素化才能发挥活性。这些结果表明，更高水平的甲基化不仅反映了Set 1/COMPASS募集，而且还反映了多轮转录。该模型为某些基因座或某些COMPASS突变体的非典型甲基化模式提供了一个简单的解释。Soares等人表明，H3 K4甲基化梯度是活性基因处的一种重要染色质修饰，不仅由Set 1甲基转移酶的靶向募集决定，而且还由转录频率和延伸率决定。将Set 1融合到RNA聚合酶导致整个基因中延长的H3 K4甲基化。
Various factors differentially recognize trimethylated histone H3 lysine 4 (H3K4me3) near promoters, H3K4me2 just downstream, and promoter-distal H3K4me1 to modulate gene expression. This methylation “gradient” is thought to result from preferential binding of the H3K4 methyltransferase Set1/COMPASS to promoter-proximal RNA polymerase II. However, other studies have suggested that location-specific cues allosterically activate Set1. ChIP-Seq experiments show that H3K4 methylation patterns on active genes are not universal or fixed, and change in response to both transcription elongation rate and frequency, as well as reduced COMPASS activity. Fusing Set1 to RNA polymerase II results in H3K4me2 throughout transcribed regions, and similarly extended H3K4me3 on highly transcribed genes. Tethered Set1 still requires histone H2B ubiquitylation for activity. These results show higher-level methylations reflect not only Set1/COMPASS recruitment, but also multiple rounds of transcription. This model provides a simple explanation for non-canonical methylation patterns at some loci or in certain COMPASS mutants. Soares et al. show that the H3K4 methylation gradient, an important chromatin modification at active genes, is determined not only by targeted recruitment of the Set1 methyltransferase, but also transcription frequency and elongation rate. Fusing Set1 to RNA polymerase results in extended H3K4 methylation throughout the gene.
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影响因子：
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