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Single cell Hi-C reveals cell-to-cell variability in chromosome structure

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE48262 | GEO | 2013/09/26

SECONDARY ACCESSION(S): PRJNA209421

REPOSITORIES: GEO

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Single cell Hi-C reveals cell-to-cell variability in chromosome structure

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

Characterization of chromosomal architecture in Arabidopsis thaliana by Chromosome Conformation Capture

Project description:Background: The packaging of long chromatin fibres in the nucleus poses a major challenge, as it must fulfil both physical and functional requirements. Until recently, insight into the chromosomal architecture of plants was mainly provided by cytogenetic studies. Complementary to these analyses, chromosome conformation technologies promise to refine and improve our view on chromosomal architecture and to provide a more generalised description of nuclear organization. Results: Employing circular chromosome conformation capture (4C), this study describes chromosomal architecture in Arabidopsis nuclei from a genome-wide perspective. Surprisingly, the linear organisation of chromosomes is reflected in the genome-wide interactome. In addition, we studied the interplay of the interactome and epigenetic marks and report that the heterochromatic knob on the short arm of chromosome 4 (hk4s) maintained a pericentromere-like interaction profile and interactome despite its euchromatic surrounding. Conclusion: Despite the extreme condensation that is necessary to pack the chromosomes into the nucleus, the Arabidopsis genome appears to be packed in a predictive manner, according to the following criteria: (i) heterochromatin and euchromatin represent two distinct interactomes, (ii) interactions between chromosomes correlates with the linear position on the chromosome arm, and (iii) distal chromosome regions have a higher potential to interact with other chromosomes. This study includes circular chromosome conformation capture (4C) sequencing information of 13 samples, present in two batches, each present in duplicates (A and B). The individual 4C sequencing information can be retrieved by the 4C primer sequence, given in the 4C primer information file.

2013-11-01 | E-GEOD-50181 | biostudies-arrayexpress

SCC1 interaction proteomics in Saccharomyces cerevisiae

Project description:FACT mediates cohesin function on chromatin Cohesin is a key regulator of genome architecture with roles in sister chromatid cohesion and the organisation of higher-order structures during interphase and mitosis. The recruitment and mobility of cohesin complexes on DNA are restricted by nucleosomes. Here we show that cohesin role in chromosome organization requires the histone chaperone FACT. Depletion of FACT in metaphase cells affects cohesin stability on chromatin reducing its accumulation at pericentric regions and binding on chromosome arms. Using Hi-C, we show that cohesin-dependent TAD (Topological Associated Domains)-like structures in G1 and metaphase chromosomes are disrupted in the absence of FACT. Surprisingly, sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our results uncover a role for FACT in genome organisation by facilitating cohesin dependent compartmentalization of chromosomes into loop domains.

2019-10-03 | PXD014896 | Pride

Cell cycle dynamics of chromosomal organisation at single-cell resolution

Project description:Chromosomes in proliferating metazoan cells undergo dramatic structural metamorphoses every cell cycle, alternating between a highly condensed mitotic structure facilitating chromosome segregation, and a decondensed interphase structure accommodating transcription, gene silencing and DNA replication. These cyclical structural transformations have been evident under the microscope for over a century, but their molecular-level analysis is still lacking. Here we use single-cell Hi-C to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological domains (TADs), contact insulation and long-range loops, all defined by ensemble Hi-C maps, are governed by distinct cell cycle dynamics. In particular, DNA replication correlates with build-up of compartments and reduction in TAD insulation, while loops are generally stable from G1 through S and G2. Analysing whole genome 3D structural models using haploid cell data, we discover a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data creates an essential new paradigm for the re-interpretation of chromosome conformation maps through the prism of the cell cycle.

2017-07-06 | GSE94489 | GEO

Multi-scale architecture of archaeal chromosomes

Project description:Chromosome conformation capture (3C) technologies have identified topologically associating domains (TADs) and larger A/B compartments as two salient structural features of eukaryotic chromosomes. These structures are sculpted by the combined actions of transcription and structural maintenance of chromosomes (SMC) superfamily proteins. Bacterial chromosomes fold into TAD-like chromosomal interaction domains (CIDs) but do not display A/B compartment-type organization. Here, we reveal that chromosomes of Sulfolobus archaea are organized into CID-like topological domains in addition to the larger A/B compartment-type structures that we described recently. We uncover local rules governing the identity of the topological domains. We also identify long-range loop structures which provide evidence of a hub-like structure that colocalizes genes involved in ribosome biogenesis. In addition to providing high resolution description of archaeal chromosome architectures, our data provide evidence for multiple modes of organization in prokaryotic chromosomes and yield novel insight into the evolution of eukaryotic chromosome conformation.

2020-12-28 | GSE159537 | GEO

Chromatin structure changes upon oxidative stress or UV irradiation in the yeast Saccharomyces cerevisiae

Project description:Development of molecular approaches based on chromosome conformation capture (3C) technology such as Hi-C, combined with methods for modeling and interpreting chromatin interaction data, have revolutionized the analysis of chromosome folding. Even if the impact of chromatin structure on gene expression seems likely, little is known about the dynamics of DNA compaction and the factors involved in this process still have to be determined. Using the yeast Saccharomyces cerevisiae as a model, we used Hi-C technology to evaluate how 3D chromatin structure changes during different cellular processes such as adaptation in response to stress or DNA repair. We optimized the protocol from Belton, J.M et al (1) to produce our Hi-C libraries, one from control cells, one from cells after oxidative stress and one from cells after UV irradiation. Preliminary analysis suggests that in response to oxidative stress, chromosomes tend to make more contacts in trans and less contacts in cis compared to normal condition.

2020-12-20 | E-MTAB-5825 | biostudies-arrayexpress

Loops, TADs, Compartments, and Territories are Elastic and Robust to Dramatic Nuclear Volume Swelling

Project description:Low-salt swelling of isolated chromatin fibers or nuclei has been used for decades to investigate the structural properties of chromatin. But, visible changes in chromatin appearance have not been linked to known building blocks of genome structure or features along the genome sequence. We combine low-salt swelling of isolated nuclei with genome-wide chromosome conformation capture (Hi-C) and imaging approaches to probe the effects of chromatin extension genome-wide. Photoconverted patterns on nuclei during expansion and contraction indicate that global genome structure is preserved after dramatic nuclear volume swelling, suggesting a highly elastic chromosome topology. Hi-C experiments before, during, and after nuclear swelling show changes in average contact probabilities at short length scales, reflecting the extension of the local chromatin fiber. But, surprisingly, during this large increase in nuclear volume, there is a striking maintenance of loops, TADs, active and inactive compartments, and chromosome territories. Subtle differences after expansion are observed, suggesting that the local chromatin state, protein interactions, and location in the nucleus can affect how strongly a given structure is maintained under stress. From these observations, we propose that genome topology is robust to extension of the chromatin fiber and isotropic shape change, and that this elasticity may be beneficial in physiological circumstances of changes in nuclear size and volume.

2021-08-26 | GSE182665 | GEO

Characterization of chromosomal architecture in Arabidopsis thaliana by Chromosome Conformation Capture

2013-11-01 | GSE50181 | GEO

Hi-C in D. melanogaster carrying second (CyO) and third (TM3) balancer chromosomes

Project description:We used a Drosophila melanogaster line (a "double balancer") carrying balancer chromosomes for both the second (CyO) and third (TM3) chromosomes, and crossed it to an isogenic wild-type "virginizer" line. Trans-heterozygous adults from the F1 generation were further crossed to the wild-type parental line to obtain the pool of N1 embryos. Allele-specific chromosome conformation capture (Hi-C) was used to measure changes in chromatin organization on both chromosomes.

2019-04-24 | E-MTAB-7512 | biostudies-arrayexpress

Hi-C Analyses with GENOVA: a case study with cohesin variants

Project description:Conformation capture-approaches like Hi-C can elucidate chromosome structure at a genome-wide scale. Hi-C datasets are large and require specialised software. Here, we present GENOVA: a user-friendly software package to analyse and visualise conformation capture data. GENOVA is an R-package that includes the most common Hi-C analyses, such as compartment and insulation score analysis. It can create annotated heatmaps to visualise the contact frequency at a specific locus and aggregate Hi-C signal over a user-specified genomic regions such as ChIP-seq data. Finally, our package supports output from the major mapping-pipelines. We demonstrate the capabilities of GENOVA by analysing Hi-C data from HAP1 cell lines in which the cohesin-subunits SA1 and SA2 were knocked out. We find that ΔSA1 cells gain intra-TAD interactions and increase compartmentalisation. ΔSA2 cells have longer loops and a less compartmentalised genome. These results suggest that cohesinSA1 forms longer loops, while cohesinSA2 plays a role in forming and maintaining intra-TAD interactions. The differences in loop-forming activity affect whole chromosome organisation consistent with a model where loops and compartments counterbalance each other. We show that GENOVA is an easy to use R-package, that allows researchers to explore Hi-C data in great detail.

2021-06-03 | GSE160490 | GEO

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