Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells

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.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI4ODQ5MWUxMzY3ZjJjYzMyZGY0ZTUwNDM4ZDkzODI2YiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4NDQ3NzA5fQ.WDISeQbMars3afd3xU31ad0as2CapR6MBdvrmShLZbNLL7pc4Oa_VcEGoid_8nFRk8gToTt_3kYc1VG3v53Dp3VPaqIy-d5IFFkTbJdYat98x2tWpWt6ONCnsutlxJI_Il6mHghaVyN8qydH-fumo9rQ_uLcfIWaVkgcmSs1YFmIj5IxiAlo0WQNe2ckYcP4hP2AM-VJvaLwOyGINV8Z78bXOw73T0RROTCsI6K5HfTTtleYucPrYM4NLiV2Jl7BM50WQYNPtJZRWmFvAHdCqPh1Cf3CFxSMWblyFINEwDfQhB7L7lN8jlQAO-DGSgRGoqmWnmG6eqcZUGQTFybHXA(mp4, (21.94 MB) Download video