Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
Kind, Jop ; Pagie, Ludo ; de Vries, Sandra S. ; Nahidiazar, Leila ; Dey, Siddharth S. ; Bienko, Magda ; Zhan, Ye ; Lajoie, Bryan ; de Graaf, Carolyn A. ; Amendola, Mario ... show 7 more
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Abstract
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 consisting 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, the 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.
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Cell. 2015 Sep 24;163(1):134-47. doi: 10.1016/j.cell.2015.08.040. Epub 2015 Sep 10. Link to article on publisher's site