Two ways to fold the genome during the cell cycle: insights obtained with chromosome conformation capture.

Two ways to fold the genome during the cell cycle: insights obtained with chromosome conformation capture.
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DOI:
10.1186/1756-8935-7-25
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发表时间:
2014
影响因子:
3.9
通讯作者:
Dekker J
Dekker J
中科院分区:
生物学2区
文献类型:
--
作者:
Dekker J

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通过有丝分裂的遗传和表观遗传对于分裂细胞维持其状态至关重要。这一过程发生在大规模重组的背景下,染色体构象在前期导致有丝分裂染色体的形成,并在重组的间期核在末期和早期G1。这篇综述强调了最近的研究在过去5年中采用染色体构象捕获结合经典模型的染色体组织的基础上几十年的显微镜观察,提供了新的见解的三维组织内的染色质间期核和有丝分裂染色体。一个引人注目的观察结果是,间期基因组组织显示与细胞类型特异性基因表达相关的细胞类型特异性特征,而有丝分裂染色体折叠似乎是普遍的和组织不变的。这就提出了一个问题,即基因组折叠是否需要表观遗传记忆。在本文中,回顾了哺乳动物基因组的两种不同的折叠状态,然后讨论了其中细胞类型特异性基因组折叠的指令在线性基因组中局部编码并通过有丝分裂传递的模型,例如,作为开放的染色质位点,有或没有转录因子的连续结合。在下一个细胞周期中,这些指令用于在调节元件上重新组装蛋白质复合物,然后通过局部作用和自组装将基因组从下向上驱动三维折叠成更高级别的细胞类型特异性组织。在这个模型中,没有明确的表观遗传记忆细胞类型特异性染色体折叠是必需的。
Genetic and epigenetic inheritance through mitosis is critical for dividing cells to maintain their state. This process occurs in the context of large-scale re-organization of chromosome conformation during prophase leading to the formation of mitotic chromosomes, and during the reformation of the interphase nucleus during telophase and early G1. This review highlights how recent studies over the last 5 years employing chromosome conformation capture combined with classical models of chromosome organization based on decades of microscopic observations, are providing new insights into the three-dimensional organization of chromatin inside the interphase nucleus and within mitotic chromosomes. One striking observation is that interphase genome organization displays cell type-specific features that are related to cell type-specific gene expression, whereas mitotic chromosome folding appears universal and tissue invariant. This raises the question of whether or not there is a need for an epigenetic memory for genome folding. Herein, the two different folding states of mammalian genomes are reviewed and then models are discussed wherein instructions for cell type-specific genome folding are locally encoded in the linear genome and transmitted through mitosis, e.g., as open chromatin sites with or without continuous binding of transcription factors. In the next cell cycle these instructions are used to re-assemble protein complexes on regulatory elements which then drive three-dimensional folding of the genome from the bottom up through local action and self-assembly into higher order levels of cell type-specific organization. In this model, no explicit epigenetic memory for cell type-specific chromosome folding is required.
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