BioProject

Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). More...

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 ~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 are more sensitive to a change 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, single-cell gene expression and chromatin accessibility analysis shows that loci with consistent NL contacts are expressed at lower levels and are more consistently inaccessible than loci with lower contact frequencies. These results highlight fundamental principles of single cell chromatin organization. Overall design: LaminB1-chromatin interactions were assayed in human KBM7 by viral transductions with Dam-Lamn B1 and Dam-only constructs. There were 2 biological replicates, hybridized in a dye-swap design Less...