Genome-wide maps of nuclear lamina interactions in single human cells.
Genome-wide maps of nuclear lamina interactions in single human cells.
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DOI：
10.1016/j.cell.2015.08.040
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发表时间：
2015-09-24
期刊：
影响因子：
64.5
通讯作者：
van Steensel B
中科院分区：
文献类型：
--
作者：
Kind J;Pagie L;de Vries SS;Nahidiazar L;Dey SS;Bienko M;Zhan Y;Lajoie B;de Graaf CA;Amendola M;Fudenberg G;Imakaev M;Mirny LA;Jalink K;Dekker J;van Oudenaarden A;van Steensel B
哺乳动物间期染色体通过数百个大的核纤层相关结构域（LAD）与核纤层（NL）相互作用。我们报告了一种在单个人类细胞中定位NL接触者全基因组的方法。近400个地图的分析揭示了一个核心架构的基因穷人的LAD接触NL与高细胞间的一致性，穿插的LAD与更多的变量NL的相互作用。可变接触往往是细胞类型特异性的，并且比一致接触对基因组倍性的变化更敏感。单细胞图表明，NL接触涉及多价相互作用超过数百个酶。此外，我们观察到广泛的染色体内协调NL接触，甚至超过几十兆碱基。如Hi-C所检测到的，这样的协调基因座表现出优先相互作用。最后，NL接触的一致性与单细胞中的基因活性呈负相关，并与异染色质组蛋白修饰H3 K9 me 3呈正相关。这些结果突出了单细胞染色质组织的基本原则。
Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, consistency of NL contacts is inversely linked to gene activity in single cells, and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single cell chromatin organization.