Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160490 | GEO | 2021/06/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Hi-C map of the three-dimensional genome organization

Project description:The spatial arrangement of interphase chromosomes in the nucleus is important for gene expression and genome function in animals and in plants. The recently developed Hi-C technology is an efficacious method to investigate genome packing. Here we present a detailed Hi-C map of the three-dimensional genome organization of the plant Arabidopsis thaliana. We find that local chromatin packing differs from the patterns seen in animals, with kilobasepair-sized segments that have much higher intra-chromosome interaction rates than neighboring regions and which represent a dominant local structural feature of genome conformation in A. thaliana. These regions appear as positive strips on two-dimensional representations of chromatin interaction and they are enriched in epigenetic marks H3K27me3, H3.1 and H3.3. We also identify over 400 insulator-like regions. Furthermore, although topologically associating domains (TADs), which are prominent in animals, are not the dominant feature of A. thaliana genome packing, we found over 1,000 regions that have properties of TAD boundaries, and a similar number of regions similar to the interior of TADs. These insulator-like, TAD-boundary-like, and TAD-interior-like regions show strong enrichment for distinct epigenetic marks, and correlate with gene transcription levels. We conclude that epigenetic modifications, gene density, and transcriptional activity all contribute to shaping the local structure of the A. thaliana nuclear genome.

2014-09-24 | E-MTAB-4438 | biostudies-arrayexpress

Computational prediction of CTCF/cohesin-based intra-TAD (sbTAD) loops that insulate chromatin contacts and gene expression in mouse liver

Project description:This SuperSeries is composed of the SubSeries listed below, and presents the high throuput sequencing datasets that were generated as part of a larger study that investigates the role of CTCF and cohesin as key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. This study presents and validates a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues. The intra-TAD loops are proposed to be formed by the same loop extrusion mechanism as the larger TAD loops; their shorter length enables finer regulatory control in restricting enhancer-promoter interactions, which enables selective, high-level expression of gene targets of super-enhancers and genes located within repressive nuclear compartments. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity.

2018-05-11 | GSE102999 | GEO

Epithelial cells in 2D and 3D culture exhibit significant differences in long-range genomic interactions

Project description:Recent studies have characterized the genomic structures of many eukaryotic cells, often with a focus on their relation to gene expression. So far, these studies have largely only investigated cells grown in 2D culture, although the transcriptomes of 3D cultured cells are generally closer to their in vivo phenotype. To examine the effects of spatial constraints on chromosome conformation, we investigated the genomic architecture of mouse hepatocytes grown in 2D and 3D cultures using in situ Hi-C. Our results reveal significant differences in long-range genomic interactions, notably in compartment identity and strength as well as in TAD-TAD interactions, but only minor differences at the TAD level. RNA-seq analysis reveals an up-regulation in the 3D cultured cells of those genes involved in physiological hepatocyte functions. We find that these genes are associated with only a subset of the structural changes, suggesting that the differences in genomic structure are indeed critically important for transcriptional regulation but also that there are major structural differences owing to other functions than gene expression. Overall, our results indicate that growth in 3D significantly alters longer-range genomic interactions, which may be consequential for a subset of genes that are important for the physiological functioning of the cell.

2020-09-30 | E-MTAB-8303 | biostudies-arrayexpress

Capturing pairwise and multi-way chromosomal conformations using C-walks

Project description:Chromosomes are folded into highly compacted structures to accommodate physical constraints within nuclei and to regulate access to genomic information. Recently, global mapping of pairwise contacts showed that loops anchoring topological domains (TADs), are highly conserved between cell types and species. Whether pairwise loops synergize to form higher order structures is still unclear. Here we develop a conformation capture approach to study higher order organization using chromosomal walks (C-walks) that link multiple genomic loci together into proximity chains. The data captured a hierarchical chromosomal structure at varying scales. Inter-chromosomal contacts constitute only 7-10% of the pairs and are restricted by the TAD structure of the interfacing chromosomes. About half of the C-walks stay within one chromosome, and almost half of these are restricted to intra-TAD spaces. Analysis of nested topological motifs suggests hierarchical chromosomal structure is present also within TADs. Targeted analysis of thousands of 3-walks anchored at strongly expressed genes support nested, rather than hub-like, chromosomal topology at active loci. Polycomb-repressed HOX domains are shown by the same approach to form synergistic hubs. Together, the data suggest that chromosomal territories, TADs, and intra-TAD loops are primarily driven by nested, possibly dynamic, pairwise contacts.

2016-02-04 | GSE77553 | GEO

Genome models integrating chromatin contacts and nuclear lamin-genome interactions reveal implications of laminopathy-causing lamin mutations on genome architecture

Project description:Processes shaping the 3-dimensional (3D) human genome remain elusive. We present Chrom3D, a user-friendly 3D whole-genome modeling software that dynamically simulates the radial positioning of topological domains (TADs) in the nucleus. We integrate Hi-C and lamin-associated domain (LAD) information to generate high-resolution ensembles of models that recapitulate single-cell TAD distribution. Chrom3D reveals dynamic TADs and TADs constitutively placed at the nuclear periphery or nuclear interior. TAD stability in these compartments is consistent with differences in TAD gene density and expression level. A- and B-type lamins as radial constraints differentially skew LAD distribution towards the nuclear interior or periphery. Predictions of radial LAD placement in model ensembles are validated by quantitative imaging. Chrom3D models reveal unexpected features of LAD regulation in the nuclear interior in cells from laminopathy patients with a LMNA mutation. Integration of radial positioning constraints in 3D genome models enables the study spatial gene regulation in disease contexts.

2016-12-22 | GSE81671 | GEO

Cohesin-dependent compaction of mitotic chromosomes in budding yeast

Project description:The extreme length of chromosomal DNA requires organizing mechanisms to both promote functional genetic interactions and ensure faithful chromosome segregation when cells divide. Microscopy and genome wide contact frequency (Hi-C) analyses indicate that intra-chromosomal looping of DNA is a primary pathway of chromosomal organization during all stages of the cell cycle (Dekker, J. & Mirny, L. . Cell 164, 1110–1121 (2016). Although the enzymatic pathways required for DNA loop formation are yet to be fully characterized, the activity of the SMC family of proteins has been consistently associated with this process in interphase and mitosis. Here we use Hi-C to study the reorganization of budding yeast chromosome conformation in early mitosis and the role of SMCs in this process. Using polymer simulations, we find that the differences between interphase and mitotic Hi-C maps can be explained by the formation of intra-chromosomal (cis-) loops in mitotic chromosomes. We demonstrate that mitotic SMC cohesin activity is required for formation of cis-loops, independently of sister-chromatid cohesion. In contrast, SMC condensin is not required for loop formation in these early mitotic cells. Rather condensin activity promotes distinct higher order structures in the chromosomes at centromeres and in the rDNA proximal regions. Thus we demonstrate that cohesin-dependent cis-loops provide the primary higher order organization of budding yeast mitotic chromosomes, independently of condensin and sister chromatid cohesion.

2017-03-22 | GSE87311 | GEO

Cell-of-origin specific 3D genome structure acquired during somatic cell reprogramming [HiC-Seq]

Project description:We studied genome topology dynamics during reprogramming of different somatic cell types with highly distinct genome conformations. We find large-scale TAD repositioning and alterations of tissue-restricted genomic neighborhoods and chromatin loops, effectively erasing the somatic cell specific genome structures while establishing an embryonic stem cell-like 3D genome. Yet, early passage iPSCs carry topological hallmarks that enable discerning their cell-of-origin. These hallmarks are not remnants of somatic chromosome topologies. Instead, the distinguishing topological features are acquired during reprogramming, as we also find for cell-of-origin dependent gene expression patterns. Hi-C was performed in somatic cells (NSC, macrophages, MEFs and pre-B cells) and their corresponding early and late induced pluripotent stem cells. In addition Hi-C was performed in E14 embryonic stem cells

2016-03-01 | E-GEOD-76479 | biostudies-arrayexpress

Differential Contribution of Steady-State RNA and Active Transcription in Chromatin Organization

Project description:Nuclear RNA and the act of transcription have been implicated in nuclear organization. However, their global contribution to shaping fundamental features of higher-order genome structure such as topologically associated domains (TADs) and genomic compartments remains unclear. To investigate these questions, we perform Hi-C genome-wide chromatin conformation capture in the presence and absence of RNase before and after crosslinking, or a transcriptional inhibitor. TAD boundaries are largely unaffected by RNase treatment, whereas transcriptional inhibition leads to higher inter-TAD interactions. Collectively, our findings demonstrate differences in the relative contribution of RNA and transcription to the formation of TAD boundaries detected by the widely used Hi-C methodology.

2019-04-01 | GSE114337 | GEO

HI-C 2.0: AN OPTIMIZED HI-C PROCEDURE FOR HIGH-RESOLUTION GENOME-WIDE MAPPING OF CHROMOSOME CONFORMATION

Project description:Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (Kb) resolution. It also includes steps to reduce random ligation and the generation of uninformative molecules, such as unligated ends, to improve the amount of valid intra-chromosomal read pairs. This protocol allows for obtaining information on conformational structures such as compartment and topologically associating domains, as well as high-resolution conformational features such as DNA loops.

2018-04-24 | GSE98161 | GEO

Co-location of chromatin loop anchors with the gene transcription machinery in maize.

Project description:We report the use of ultra-high Hi-C sequencing to characterize TAD-like domains and chromatin loops in maize, along with their co-location characteristics with open chromatin (ATAC-Seq) peaks and gene expreesion (mRNA-Seq) data generated from the same tissue samples.

2020-11-12 | GSE161294 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data