Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Genomics | Molecular Biology | Systems Biology
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.
DOI of Published Version
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
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. (2015). Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells. Systems Biology Publications. https://doi.org/10.1016/j.cell.2015.08.040. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/77