Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark; Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: https://twitter.com/@ValeFlury.
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark; Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
Curr Opin Genet Dev. 2024 Apr;85:102161. doi: 10.1016/j.gde.2024.102161. Epub 2024 Mar 5.
Sustaining cell identity and function across cell division is germane to human development, healthspan, and cancer avoidance. This relies significantly on propagation of chromatin organization between cell generations, as chromatin presents a barrier to cell fate and cell state conversions. Inheritance of chromatin states across the many cell divisions required for development and tissue homeostasis represents a major challenge, especially because chromatin is disrupted to allow passage of the DNA replication fork to synthesize the two daughter strands. This process also leads to a twofold dilution of epigenetic information in histones, which needs to be accurately restored for faithful propagation of chromatin states across cell divisions. Recent research has identified distinct multilayered mechanisms acting to propagate epigenetic information to daughter strands. Here, we summarize key principles of how epigenetic information in parental histones is transferred across DNA replication and how new histones robustly acquire the same information postreplication, representing a core component of epigenetic cell memory.
维持细胞的身份和功能在细胞分裂中至关重要,这对于人类的发育、健康和癌症预防都具有重要意义。这在很大程度上依赖于染色质组织在细胞世代之间的传播,因为染色质是细胞命运和细胞状态转换的障碍。在发育和组织稳态所需的许多细胞分裂中,染色质状态的遗传是一个主要的挑战,特别是因为染色质被打乱,以允许 DNA 复制叉通过,合成两个子链。这个过程还导致组蛋白中表观遗传信息的两倍稀释,需要准确地恢复,以实现染色质状态在细胞分裂中的忠实传播。最近的研究已经确定了不同的多层次机制,用于将表观遗传信息传递到子链。在这里,我们总结了亲本组蛋白中的表观遗传信息如何在 DNA 复制过程中转移,以及新的组蛋白如何在后复制过程中稳健地获得相同的信息,这代表了表观遗传细胞记忆的核心组成部分。