Single-Cell Dynamics of Genome-Nuclear Lamina Interactions
Single-Cell Dynamics of Genome-Nuclear Lamina Interactions
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DOI：
10.1016/j.cell.2013.02.028
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发表时间：
2013-03-28
期刊：
影响因子：
64.5
通讯作者：
van Steensel, Bas
中科院分区：
文献类型：
--
作者：
Kind, Jop;Pagie, Ludo;van Steensel, Bas
核层（NL）与数百个称为层相关结构域（LADs）的大基因组区域相互作用。这些相互作用的动力学以及与表观遗传修饰的关系尚不清楚。我们使用“分子接触记忆”方法可视化了单细胞中LADs的命运。在每个细胞核中，只有大约30%的lad位于周围；这些lad与NL有间歇性的分子接触，但仍然局限于周围。有丝分裂时，LAD的位置不能被检测到遗传，而是随机重新洗牌。单个LADs与NL的接触与单细胞中的转录抑制和H3K9二甲基化有关。此外，我们发现H3K9甲基转移酶G9a是NL接触的调节因子。总的来说，这些结果突出了与基因调控有关的染色体动态空间结构原理。
The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a "molecular contact memory" approach. In each nucleus, only similar to 30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL is linked to transcriptional repression and H3K9 dimethylation in single cells. Furthermore, we identify the H3K9 methyltransferase G9a as a regulator of NL contacts. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes in relation to gene regulation.