Nucleosome Turnover Regulates Histone Methylation Patterns over the Genome
Nucleosome Turnover Regulates Histone Methylation Patterns over the Genome
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DOI：
10.1016/j.molcel.2018.10.028
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发表时间：
2019-01-03
期刊：
影响因子：
16
通讯作者：
Crabtree, Gerald R.
中科院分区：
文献类型：
--
作者：
Chory, Emma J.;Calarco, Joseph P.;Crabtree, Gerald R.
最近的研究表明，核小体周转速度很快，每个细胞周期会发生几次。为了了解核小体周转对表观遗传景观的影响，我们研究了 H3K79 甲基化，它是由单一甲基转移酶 (Dot1l) 产生的，没有已知的去甲基化酶。使用化学诱导邻近 (CIP)，我们发现 H3K79 甲基化的价态（单、二和三）由核小体周转率决定。此外，该标记的传播是通过基因组上的核小体周转模拟预测的，并解释了 H3K79me 向转录单元的不对称分布。更广泛地说，对其他保守组蛋白修饰的荟萃分析表明，核小体周转模型可以预测甲基化标记的价态和染色体传播。基于来自蠕虫、果蝇和小鼠的数据，我们提出修饰核小体的周转是表观遗传标记传播的一般手段和甲基化价的决定因素。
Recent studies have indicated that nucleosome turnover is rapid, occurring several times per cell cycle. To access the effect of nucleosome turnover on the epigenetic landscape, we investigated H3K79 methylation, which is produced by a single methyltransferase (Dot1l) with no known demethylase. Using chemical-induced proximity (CIP), we find that the valency of H3K79 methylation (mono-, di-, and tri-) is determined by nucleosome turnover rates. Furthermore, propagation of this mark is predicted by nucleosome turnover simulations over the genome and accounts for the asymmetric distribution of H3K79me toward the transcriptional unit. More broadly, a meta-analysis of other conserved histone modifications demonstrates that nucleosome turnover models predict both valency and chromosomal propagation of methylation marks. Based on data from worms, flies, and mice, we propose that the turnover of modified nucleosomes is a general means of propagation of epigenetic marks and a determinant of methylation valence.