Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA; Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mol Cell. 2019 Jan 3;73(1):61-72.e3. doi: 10.1016/j.molcel.2018.10.028. Epub 2018 Nov 21.
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.
最近的研究表明核小体周转率很快，每个细胞周期中发生几次。为了研究核小体周转率对表观遗传景观的影响，我们研究了 H3K79 甲基化，它由一种单一的甲基转移酶（Dot1l）产生，没有已知的去甲基酶。使用化学诱导的接近（CIP），我们发现 H3K79 甲基化（单、二和三）的价态由核小体周转率决定。此外，基因组上的核小体周转率模拟预测了这种标记的传播，并解释了 H3K79me 向转录单位的不对称分布。更广泛地说，对其他保守组蛋白修饰的荟萃分析表明，核小体周转率模型预测了甲基化标记的价态和染色体传播。基于来自蠕虫、苍蝇和老鼠的数据，我们提出，修饰核小体的周转率是表观遗传标记传播的一种通用手段，也是甲基化价态的决定因素。
