SRA

Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation by integrating, for the first time, allele-specific data obtained by high-throughput single-cell RNA-seq, ATAC-seq, and Hi-C. In differentiated cells, contact decay profiles, which clearly distinguish the active and inactive X chromosomes, reveal loss of the inactive X-specific structure at mitosis followed by a rapid reappearance, suggesting a bookkeeping mechanism. In differentiating embryonic stem cells, changes in contact decay profiles are detected in parallel on both the X chromosomes and autosomes, suggesting profound simultaneous reorganization. The onset of the inactive X-specific structure in single cells is notably delayed relative to that of gene silencing, consistent with the idea that chromatin compaction is a late event of X inactivation. Novel computational approaches to effectively align single-cell gene expression, chromatin accessibility, and 3D chromosome structure reveal that long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility. ### Competing Interest Statement The authors have declared no competing interest. Overall design: lab: Christine Disteche, UW award: 1U54DK107979-01 accession: 4DNESB7XYI9V submitted_by: Giancarlo Bonora dataset_label: sci-Hi-C on mESCs differentiated to embryoid body contributing_labs: William Noble, UW, Zhijun Duan, UW, Jay Ashok Shendure, UW experiment_type: sci-Hi-C url: https://data.4dnucleome.org/experiment-sets/4DNESB7XYI9V/ number_of_experiments: 23 experiment: 4DNEXOA4DNR8; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXCDN76F9; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXJ33QCZU; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXLCFXRUP; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEX1BY7H2C; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXU9FJ24U; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXTJOSWTW; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXMYV77X1; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXK2CP3J1; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXXNEYDTM; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXJNGKL32; replicate_number: Biorep 2, Techrep 1 experiment: 4DNEXJAHCEIN; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXLZWN9VH; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXV3C383J; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXB7EWKCM; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXTLVDZQP; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXEE1N4JI; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXPLD13JA; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXVG7LXZE; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXWHKWMSY; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXRMWXOKT; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXMN3ZJ4X; replicate_number: Biorep 1, Techrep 1 experiment: 4DNEXMNAHJPG; replicate_number: Biorep 2, Techrep 1 Series supplementary files: *************** genome_assembly: GRCm38 description: A tarball containing processed sci-Hi-C data. file name: 4DNFIZ8TEE2M.tar file_format: tar *************** file_type: readme description: A text file describing the contents and processing steps for the sci-Hi-C processed data in 4DNFIZ8TEE2M. file name: 4DNFI7QQWLOV.txt file_format: txt *************** file_type: directory tree description: A text file with a directory tree for the sci-Hi-C processed data in 4DNFIZ8TEE2M. file name: 4DNFICOPS6ER.txt file_format: txt