Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, U.K.
Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
Biochem Soc Trans. 2020 Dec 18;48(6):2891-2902. doi: 10.1042/BST20200873.
The concept of cellular plasticity is particularly apt in early embryonic development, where there is a tug-of-war between the stability and flexibility of cell identity. This balance is controlled in part through epigenetic mechanisms. Epigenetic plasticity dictates how malleable cells are to change by adjusting the potential to initiate new transcriptional programmes. The higher the plasticity of a cell, the more readily it can adapt and change its identity in response to external stimuli such as differentiation cues. Epigenetic plasticity is regulated in part through the action of epigenetic priming factors which establish this permissive epigenetic landscape at genomic regulatory elements to enable future transcriptional changes. Recent studies on the DNA binding proteins Developmental Pluripotency Associated 2 and 4 (Dppa2/4) support their roles as epigenetic priming factors in facilitating cell fate transitions. Here, using Dppa2/4 as a case study, the concept of epigenetic plasticity and molecular mechanism of epigenetic priming factors will be explored. Understanding how epigenetic priming factors function is key not only to improve our understanding of the tight control of development, but also to give insights into how this goes awry in diseases of cell identity, such as cancer.
细胞可塑性的概念在早期胚胎发育中尤为恰当,因为在这个过程中,细胞身份的稳定性和灵活性之间存在着一场拉锯战。这种平衡在一定程度上受到表观遗传机制的控制。表观遗传可塑性通过调节启动新转录程序的潜力来决定细胞的可塑性,从而影响细胞的可变性。细胞的可塑性越高,它就越能适应外部刺激,如分化信号,并改变其身份。表观遗传可塑性部分受到表观遗传启动因子的作用的调节,这些因子在基因组调控元件上建立这种允许的表观遗传景观,以实现未来的转录变化。最近关于 DNA 结合蛋白发育多能性相关蛋白 2 和 4(Dppa2/4)的研究支持它们作为表观遗传启动因子在促进细胞命运转变中的作用。在这里,我们将以 Dppa2/4 为例,探讨表观遗传可塑性的概念和表观遗传启动因子的分子机制。了解表观遗传启动因子的功能不仅是深入了解发育严格控制的关键,也是深入了解细胞身份疾病(如癌症)中这种控制失常的关键。