Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics.

ABSTRACT: Nuclear compartmentalization of active and inactive chromatin is thought to occur through microphase separation mediated by interactions between loci of similar type. The nature and dynamics of these interactions are not known. We developed liquid chromatin Hi-C to map the stability of associations between loci. Before fixation and Hi-C, chromosomes are fragmented, which removes strong polymeric constraint, enabling detection of intrinsic locus-locus interaction stabilities. Compartmentalization is stable when fragments are larger than 10-25 kb. Fragmentation of chromatin into pieces smaller than 6 kb leads to gradual loss of genome organization. Lamin-associated domains are most stable, whereas interactions for speckle- and polycomb-associated loci are more dynamic. Cohesin-mediated loops dissolve after fragmentation. Liquid chromatin Hi-C provides a genome-wide view of chromosome interaction dynamics.

SUBMITTER: Belaghzal H

PROVIDER: S-EPMC7946813 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C

Project description:Chromosomes are folded so that active and inactive chromatin domains are spatially segregated to form a variety of sub-nuclear neighborhoods. Compartmentalization is thought to occur through polymer phase/microphase separation mediated by interactions between loci of similar type. The nature and dynamics of these interactions are not known. We developed liquid chromatin Hi-C to map the stability of associations between loci genome-wide. Before fixation and Hi-C, chromosomes are fragmented removing the strong polymeric constraint to enable detection of intrinsic locus-locus interaction stabilities. We find that chromosome compartmentalization is dependent on the length of chromatin fragments. Compartmentalization is stable when fragments are over 10-25 kb. Fragmenting chromatin into pieces smaller than 6 kb leads to gradual loss of spatial genome organization. In addition to fragmentation level dissolution kinetics of chromatin interactions vary for different chromatin domains. Lamin associated domains are most stable, and speckle-associated loci are more dynamic. The polycomb-enriched B1 sub-compartment also displays highly unstable interactions. Cohesin-mediated loops dissolve after fragmentation, possibly because cohesin rings slide off nearby DNA ends. Liquid chromatin Hi-C provides a genome-wide view of chromosome interaction dynamics, revealing a range of conformational stabilities at different sub-nuclear structures.

2020-12-11 | GSE134590 | GEO

Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C

Project description:Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C

| PRJNA555717 | ENA

DeCOOC Deconvoluted Hi-C Map Characterizes the Chromatin Architecture of Cells in Physiologically Distinctive Tissues.

Project description:Deciphering variations in chromosome conformations based on bulk three-dimensional (3D) genomic data from heterogenous tissues is a key to understanding cell-type specific genome architecture and dynamics. Surprisingly, computational deconvolution methods for high-throughput chromosome conformation capture (Hi-C) data remain very rare in the literature. Here, a deep convolutional neural network (CNN), deconvolve bulk Hi-C data (deCOOC) that remarkably outperformed all the state-of-the-art tools in the deconvolution task is developed. Interestingly, it is noticed that the chromatin accessibility or the Hi-C contact frequency alone is insufficient to explain the power of deCOOC, suggesting the existence of a latent embedded layer of information pertaining to the cell type specific 3D genome architecture. By applying deCOOC to in-house-generated bulk Hi-C data from visceral and subcutaneous adipose tissues, it is found that the characteristic chromatin features of M2 cells in the two anatomical loci are distinctively bound to different physiological functionalities. Taken together, deCOOC is both a reliable Hi-C data deconvolution method and a powerful tool for functional extraction of 3D genome architecture.

| S-EPMC10520690 | biostudies-literature

Chromatin compartment dynamics in a haploinsufficient model of cardiac laminopathy.

Project description:Mutations in A-type nuclear lamins cause dilated cardiomyopathy, which is postulated to result from dysregulated gene expression due to changes in chromatin organization into active and inactive compartments. To test this, we performed genome-wide chromosome conformation analyses in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with a haploinsufficient mutation for lamin A/C. Compared with gene-corrected cells, mutant hiPSC-CMs have marked electrophysiological and contractile alterations, with modest gene expression changes. While large-scale changes in chromosomal topology are evident, differences in chromatin compartmentalization are limited to a few hotspots that escape segregation to the nuclear lamina and inactivation during cardiogenesis. These regions exhibit up-regulation of multiple noncardiac genes including CACNA1A, encoding for neuronal P/Q-type calcium channels. Pharmacological inhibition of the resulting current partially mitigates the electrical alterations. However, chromatin compartment changes do not explain most gene expression alterations in mutant hiPSC-CMs. Thus, global errors in chromosomal compartmentation are not the primary pathogenic mechanism in heart failure due to lamin A/C haploinsufficiency.

| S-EPMC6719452 | biostudies-literature

Capturing cell type-specific chromatin compartment patterns by applying topic modeling to single-cell Hi-C data.

Project description:Single-cell Hi-C (scHi-C) interrogates genome-wide chromatin interaction in individual cells, allowing us to gain insights into 3D genome organization. However, the extremely sparse nature of scHi-C data poses a significant barrier to analysis, limiting our ability to tease out hidden biological information. In this work, we approach this problem by applying topic modeling to scHi-C data. Topic modeling is well-suited for discovering latent topics in a collection of discrete data. For our analysis, we generate nine different single-cell combinatorial indexed Hi-C (sci-Hi-C) libraries from five human cell lines (GM12878, H1Esc, HFF, IMR90, and HAP1), consisting over 19,000 cells. We demonstrate that topic modeling is able to successfully capture cell type differences from sci-Hi-C data in the form of "chromatin topics." We further show enrichment of particular compartment structures associated with locus pairs in these topics.

| S-EPMC7526900 | biostudies-literature

Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex.

Project description:The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains challenging. We address this by characterizing the topology of the cortical chromatin interaction network using scale-aware topological measures. We demonstrate that based on these characterizations it is possible to accurately predict spatial co-expression between genes in the mouse cortex. Consistent with previous findings, we find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. However, the accuracy of the prediction can be substantially improved when chromatin interactions are described using scale-aware topological measures of the multi-resolution chromatin interaction network. We conclude that, for co-expression prediction, it is necessary to take into account different levels of chromatin interactions ranging from direct interaction between genes (i.e. small-scale) to chromatin compartment interactions (i.e. large-scale).

| S-EPMC4429121 | biostudies-literature

Chromatin-interaction compartment switch at developmentally regulated chromosomal domains reveals an unusual principle of chromatin folding.

Project description:Several 400- to 800-kb murine chromosome domains switch from early to late replication during loss of pluripotency, accompanied by a stable form of gene silencing that is resistant to reprogramming. We found that, whereas enhanced nuclease accessibility correlated with early replication genome-wide, domains that switch replication timing during differentiation were exceptionally inaccessible even when early-replicating. Nonetheless, two domains studied in detail exhibited substantial changes in transcriptional activity and higher-order chromatin unfolding confined to the region of replication timing change. Chromosome conformation capture (4C) data revealed that in the unfolded state in embryonic stem cells, these domains interacted preferentially with the early-replicating chromatin compartment, rarely interacting even with flanking late-replicating domains, whereas after differentiation, these same domains preferentially associated with late-replicating chromatin, including flanking domains. In both configurations they retained local boundaries of self-interaction, supporting the replication domain model of replication-timing regulation. Our results reveal a principle of developmentally regulated, large-scale chromosome folding involving a subnuclear compartment switch of inaccessible chromatin. This unusual level of regulation may underlie resistance to reprogramming in replication-timing switch regions.

| S-EPMC3411983 | biostudies-literature

Identification of chromatin loops from Hi-C interaction matrices by CTCF-CTCF topology classification.

Project description:Genome-wide profiling of long-range interactions has revealed that the CCCTC-Binding factor (CTCF) often anchors chromatin loops and is enriched at boundaries of the so-called Topologically Associating Domains, which suggests that CTCF is essential in the 3D organization of chromatin. However, the systematic topological classification of pairwise CTCF-CTCF interactions has not been yet explored. Here, we developed a computational pipeline able to classify all CTCF-CTCF pairs according to their chromatin interactions from Hi-C experiments. The interaction profiles of all CTCF-CTCF pairs were further structurally clustered using self-organizing feature maps and their functionality characterized by their epigenetic states. The resulting clusters were then input to a convolutional neural network aiming at the de novo detecting chromatin loops from Hi-C interaction matrices. Our new method, called LOOPbit, is able to automatically detect significant interactions with a higher proportion of enhancer-promoter loops compared to other callers. Our highly specific loop caller adds a new layer of detail to the link between chromatin structure and function.

| S-EPMC8903010 | biostudies-literature

DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell.

Project description:Topologically associating domains (TAD) are a key structure of the 3D mammalian genomes. However, the prevalence and dynamics of TAD-like domains in single cells remain elusive. Here we develop a new algorithm, named deTOKI, to decode TAD-like domains with single-cell Hi-C data. By non-negative matrix factorization, deTOKI seeks regions that insulate the genome into blocks with minimal chance of clustering. deTOKI outperforms competing tools and reliably identifies TAD-like domains in single cells. Finally, we find that TAD-like domains are not only prevalent, but also subject to tight regulation in single cells.

| S-EPMC8314462 | biostudies-literature

CscoreTool: fast Hi-C compartment analysis at high resolution.

Project description:Summary:The genome-wide chromosome conformation capture (Hi-C) has revealed that the eukaryotic genome can be partitioned into A and B compartments that have distinctive chromatin and transcription features. Current Principle Component Analyses (PCA)-based method for the A/B compartment prediction based on Hi-C data requires substantial CPU time and memory. We report the development of a method, CscoreTool, which enables fast and memory-efficient determination of A/B compartments at high resolution even in datasets with low sequencing depth. Availability and implementation:https://github.com/scoutzxb/CscoreTool. Contact:xzheng@carnegiescience.edu. Supplementary information:Supplementary data are available at Bioinformatics online.

| S-EPMC5925784 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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