Modeling the Dynamics of Bivalent Histone Modifications

Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have “bivalent domains” in which the nucleosomes contain both active (H3K4me3) and repressive (H3K27me3) marks. It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear. Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns. We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states.

组蛋白的表观遗传修饰可能促进邻近基因转录的激活或抑制。近期实验研究表明，干细胞中许多谱系控制基因的启动子具有‘二价域’，其中核小体同时含有激活标记（H3K4me3）和抑制标记（H3K27me3）。普遍认为，二价域在干细胞分化过程中扮演着至关重要的角色，但其潜在机制尚不明确。在此，我们构建了一个数学模型以探究组蛋白修饰模式的动态特性。随后，我们阐述我们的建模框架能够捕捉到实验观察到的组合染色质状态的显著特征。