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.

2013-09-26 | E-GEOD-48262 | biostudies-arrayexpress

3D Chromosome Structure Can Reveal Stem Cell Signatures

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-20 | GSE126014 | GEO

3D chromatin structure in colon cancer

Project description:We report the application of in situ Hi-C technology to 40 colorectal cancer patients and 10 paried-normal tissue to indentify CRC specific changes in 3D chromatin structure. The chromatin contact matrix 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 matrix. The tumor specific 3D chromatin sturcutre changes and the enhancer-promoter rewiring mediated by the identified chromatin sturcture changes were analyzed. The complex chromosome-wide rearrangements such as chromothripsis and its effect to 3D chromatin sturucters were also observed.

2023-07-27 | GSE137188 | GEO

RNA surveillance controls 3D genome structure via stable cohesin chromosome interaction

Project description:The 3D architecture that the genome is folded into is regulated by CTCF, which determines domain borders, and cohesin, which generates interactions within domains. However, organisms lacking CTCF have been reported to still have cohesin-mediated 3D structures with strong borders. How this can be achieved and precisely regulated are yet unknown. Using in situ Hi-C, we found that 3’-end RNA processing factors coupled with proper transcription termination are a cis-acting determinant that regulates the localization and dynamics of cohesin on the chromosome arms. Loss of RNA processing factors, including nuclear exosome and Pfs2, destabilizes cohesin from the 3'-ends of convergent genes and results in decreased cohesin-mediated domain boundaries. We observed the co-localization between Rad21 and a wide range of 3'end RNA processing/termination factors. Further, deletion of Rrp6 leads to cohesin redistribution to facultative heterochromatin, resulting in improper domain boundaries. Importantly, we observed that knockdown of Rrp6Exosc10 caused a defect in cohesin binding and loss of local topologically associating domains (TADs) interactions in mouse embryonic stem cells. Based on these findings, we propose a novel function of the RNA surveillance pathway in 3D genome organization via cohesin complex, which provides the molecular basis underlying the dynamics of cohesin function.

2022-12-01 | GSE85147 | GEO

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