Zhao Wei, Qiao Lingxia, Yan Shiyu, Nie Qing, Zhang Lei
Beijing International Center for Mathematical Research, Peking University, Beijing 100871, China.
Center for Quantitative Biology, Peking University, Beijing 100871, China.
iScience. 2021 Jun 17;24(7):102732. doi: 10.1016/j.isci.2021.102732. eCollection 2021 Jul 23.
Bivalent chromatin is characterized by occupation of both activating and repressive histone modifications. Here, we develop a mathematical model that involves antagonistic histone modifications H3K4me3 and H3K27me3 to capture the key features of bivalent chromatin. Three necessary conditions for the emergence of bivalent chromatin are identified, including advantageous methylating activity over demethylating activity, frequent noise conversions of modifications, and sufficient nonlinearity. The first condition is further confirmed by analyzing the existing experimental data. Investigation of the composition of bivalent chromatin reveals that bivalent nucleosomes carrying both H3K4me3 and H3K27me3 account for no more than half of nucleosomes at the bivalent chromatin domain. We identify that bivalent chromatin not only allows transitions to multiple states but also serves as a stepping stone to facilitate a stepwise transition between repressive chromatin state and activating chromatin state and thus elucidate crucial roles of bivalent chromatin in mediating phenotypical plasticity during cell fate determination.
双价染色质的特征是同时存在激活型和抑制型组蛋白修饰。在此，我们构建了一个数学模型，该模型涉及拮抗型组蛋白修饰H3K4me3和H3K27me3，以捕捉双价染色质的关键特征。确定了双价染色质出现的三个必要条件，包括甲基化活性优于去甲基化活性、修饰的频繁噪声转换以及足够的非线性。通过分析现有实验数据进一步证实了第一个条件。对双价染色质组成的研究表明，携带H3K4me3和H3K27me3的双价核小体在双价染色质结构域中占核小体总数的比例不超过一半。我们发现双价染色质不仅允许向多种状态转变，还作为一块垫脚石，促进抑制型染色质状态和激活型染色质状态之间的逐步转变，从而阐明双价染色质在细胞命运决定过程中介导表型可塑性的关键作用。
