Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes
Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes
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DOI：
10.1016/j.celrep.2019.12.060
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发表时间：
2020-01-28
期刊：
影响因子：
8.8
通讯作者：
Groth, Anja
中科院分区：
文献类型：
--
作者：
Alabert, Constance;Loos, Carolin;Groth, Anja
染色质状态必须在细胞增殖期间维持，以维护细胞身份和基因组完整性。组蛋白修饰的遗传在这一过程中是中心的。然而，组蛋白修饰景观的挑战是在每个细胞周期中掺入新的未修饰的组蛋白，遗传性的原则仍然不清楚。我们采用定量计算建模方法来描述组蛋白H3K27和H3K36甲基化状态的传播。我们测量组合H3K27和H3K36甲基化模式，通过定量质谱法对后代的组蛋白。使用模型比较，我们拒绝主动全局去甲基化，并调用由不同的甲基化终点定义的域的存在。我们发现，H3K27me3对预先存在的组蛋白刺激从头H3K27me3建立的速率，支持在及时染色质恢复的读写机制。最后，我们提供了H3K27和H3K36甲基化之间相互拮抗作用的详细定量图片，并提出它在细胞分裂中稳定了表观遗传状态。
Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the histone modification landscape is challenged by incorporation of new unmodified histones during each cell cycle, and the principles governing heritability remain unclear. We take a quantitative computational modeling approach to describe propagation of histone H3K27 and H3K36 methylation states. We measure combinatorial H3K27 and H3K36 methylation patterns by quantitative mass spectrometry on subsequent generations of histones. Using model comparison, we reject active global demethylation and invoke the existence of domains defined by distinct methylation endpoints. We find that H3K27me3 on pre-existing histones stimulates the rate of de novo H3K27me3 establishment, supporting a read-write mechanism in timely chromatin restoration. Finally, we provide a detailed quantitative picture of the mutual antagonism between H3K27 and H3K36 methylation and propose that it stabilizes epigenetic states across cell division.