Japan Science and Technology Agency, PRESTO, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan.
Bioorg Med Chem. 2012 Mar 15;20(6):1887-92. doi: 10.1016/j.bmc.2012.01.018. Epub 2012 Jan 21.
The combination of histone posttranslational modifications occurring in nucleosomal histones determines the epigenetic code. Histone modifications such as acetylation are dynamically controlled in response to a variety of signals during the cell cycle and differentiation, but they are paradoxically maintained through cell division to impart tissue specific gene expression patterns to progeny. The dynamics of histone modifications in living cells are poorly understood, because of the lack of experimental tools to monitor them in a real-time fashion. Recently, FRET-based imaging probes for histone H4 acetylation have been developed, which enabled monitoring of changes in histone acetylation during the cell cycle and drug treatment. Further development of this type of fluorescent probes for other modifications will make it possible to visualize complicated epigenetic regulation in living cells.
组蛋白翻译后的修饰共同作用决定了表观遗传密码。组蛋白修饰，如乙酰化，在细胞周期和分化过程中会对各种信号做出动态调控，但它们会通过细胞分裂被保留下来，从而将组织特异性的基因表达模式传递给子细胞。由于缺乏实时监测这些修饰的实验工具，因此对于活细胞中组蛋白修饰的动态变化还知之甚少。最近，已经开发出基于 FRET 的组蛋白 H4 乙酰化成像探针，这使得在细胞周期和药物处理过程中监测组蛋白乙酰化的变化成为可能。进一步开发用于其他修饰的这种类型的荧光探针，将使我们能够在活细胞中可视化复杂的表观遗传调控。
