Institute for Regenerative Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; email:
Annu Rev Genomics Hum Genet. 2022 Aug 31;23:53-71. doi: 10.1146/annurev-genom-121321-094603. Epub 2022 Apr 19.
Virtually all cell types have the same DNA, yet each type exhibits its own cell-specific pattern of gene expression. During the brief period of mitosis, the chromosomes exhibit changes in protein composition and modifications, a marked condensation, and a consequent reduction in transcription. Yet as cells exit mitosis, they reactivate their cell-specific programs with high fidelity. Initially, the field focused on the subset of transcription factors that are selectively retained in, and hence bookmark, chromatin in mitosis. However, recent studies show that many transcription factors can be retained in mitotic chromatin and that, surprisingly, such retention can be due to nonspecific chromatin binding. Here, we review the latest studies focusing on low-level transcription via promoters, rather than enhancers, as contributing to mitotic memory, as well as new insights into chromosome structure dynamics, histone modifications, cell cycle signaling, and nuclear envelope proteins that together ensure the fidelity of gene expression through a round of mitosis.
实际上所有细胞类型都具有相同的 DNA,但每种类型都表现出其自身的细胞特异性基因表达模式。在短暂的有丝分裂期间,染色体表现出蛋白质组成和修饰的变化、明显的浓缩以及随之而来的转录减少。然而,当细胞退出有丝分裂时,它们以高保真度重新激活其细胞特异性程序。最初,该领域专注于在有丝分裂中选择性保留并因此标记染色质的转录因子亚组。然而,最近的研究表明,许多转录因子可以保留在有丝分裂染色质中,而且令人惊讶的是,这种保留可以归因于非特异性染色质结合。在这里,我们回顾了最新的研究,这些研究侧重于通过启动子而不是增强子进行低水平转录,这有助于有丝分裂记忆,以及对染色体结构动力学、组蛋白修饰、细胞周期信号转导和核膜蛋白的新见解,这些共同确保了一轮有丝分裂过程中基因表达的保真度。