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Close to the edge: Heterochromatin at the nucleolar and nuclear peripheries
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ( IF 2.6 ) Pub Date : 2020-12-08 , DOI: 10.1016/j.bbagrm.2020.194666
Aizhan Bizhanova 1 , Paul D Kaufman 1
Affiliation  

Chromatin is a dynamic structure composed of DNA, RNA, and proteins, regulating storage and expression of the genetic material in the nucleus. Heterochromatin plays a crucial role in driving the three-dimensional arrangement of the interphase genome, and in preserving genome stability by maintaining a subset of the genome in a silent state. Spatial genome organization contributes to normal patterns of gene function and expression, and is therefore of broad interest. Mammalian heterochromatin, the focus of this review, mainly localizes at the nuclear periphery, forming Lamina-associated domains (LADs), and at the nucleolar periphery, forming Nucleolus-associated domains (NADs). Together, these regions comprise approximately one-half of mammalian genomes, and most but not all loci within these domains are stochastically placed at either of these two locations after exit from mitosis at each cell cycle. Excitement about the role of these heterochromatic domains in early development has recently been heightened by the discovery that LADs appear at some loci in the preimplantation mouse embryo prior to other chromosomal features like compartmental identity and topologically-associated domains (TADs). While LADs have been extensively studied and mapped during cellular differentiation and early embryonic development, NADs have been less thoroughly studied. Here, we summarize pioneering studies of NADs and LADs, more recent advances in our understanding of cis/trans-acting factors that mediate these localizations, and discuss the functional significance of these associations.



中文翻译:

靠近边缘:核仁和核周边的异染色质

染色质是由 DNA、RNA 和蛋白质组成的动态结构,调节细胞核中遗传物质的储存和表达。异染色质在驱动间期基因组的三维排列以及通过维持基因组子集处于沉默状态来保持基因组稳定性方面发挥着至关重要的作用。空间基因组组织有助于基因功能和表达的正常模式,因此受到广泛关注。哺乳动物异染色质是本综述的重点,主要位于核周边,形成核层相关结构域 (LAD),并位于核仁周边,形成核仁相关结构域 (NAD)。这些区域总共包含大约一半的哺乳动物基因组,并且这些域内的大多数但不是全部基因座在每个细胞周期退出有丝分裂后随机放置在这两个位置中的任意一个位置。最近发现,LAD 在其他染色体特征(如区室身份和拓扑相关结构域 (TAD))之前出现在植入前小鼠胚胎的某些位点,这使得人们对这些异染色质结构域在早期发育中的作用更加兴奋。虽然 LAD 在细胞分化和早期胚胎发育过程中已被广泛研究和绘制,但 NAD 的研究还不够深入。在这里,我们总结了 NAD 和 LAD 的开创性研究,我们对介导这些定位的顺式/反式作用因子的理解的最新进展,并讨论了这些关联的功能意义。

更新日期:2020-12-16
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