Project description:Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single cell Hi-C, combined with genome-wide statistical analysis and structural modeling of single copy X chromosomes, to show that individual chromosomes maintain domain organisation at the megabase scale, but show variable cell-to-cell chromosome territory structures at larger scales. Despite this structural stochasticity, localisation of active gene domains to boundaries of territories is a hallmark of chromosomal conformation, affecting most domains in most nuclei. Single cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organisation underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns. Mouse Th1 single-cell Hi-C maps were produced and paired-end sequenced. 10 single-cell samples and a multi-sample pool together with a population Hi-C sample are included.
Project description:We report the application of in situ Hi-C technology to 40 colorectal cancer patients and 10 paired-normal tissue to identify CRC specific changes in 3D chromatin structure. The chromatin contact matrices were generated by the sequencing data and image processing/deep learning-based algorithm was proposed to identify long-range abnormal chromatin interaction patterns in the contact matrices. The tumor specific 3D chromatin structure changes and the enhancer-promoter rewiring mediated by the identified chromatin structure changes were analyzed. The complex chromosome-wide rearrangements such as chromothripsis and its effect to 3D chromatin structure were also observed.