Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

3D genome of multiple myeloma reveals spatial genome disorganization associated with copy number variations

ABSTRACT: Hi-C technique has been widely applied to study the three-dimensional architecture of the whole genome. Genome structures such as compartment A/B, TAD (topologically associated domain) and chromatin loops can be identified from Hi-C data in both normal cells of human and other species, and are found to be associated with features such as epigenetic markers, DNA-binding proteins and gene expression. But such technique had been rarely used in cancer studies. Here we used Hi-C to study the aneuploid cancer genomic architecture in multiple myeloma cells. Our results indicate that Hi-C interaction matrix of cancer cells is affected by CNVs and should be adjusted for copy number. After correcting this CNV bias, we found a significant overlapping between the boundaries of CNV blocks and boundaries of TADs, which suggests that TAD boundaries are fragile sites for CNV breakpoints. In addition, the compartment A/B switching is associated with differential gene expression, from which we found important genes that are related with multiple myeloma. We build a 3D structure model of the aneuploidy genome and found that there are great changes both in the whole genome spatial interactome and local chromosome territories. In summary, our research builds the first 3D genome interaction maps of multiple myeloma and the first time notice this CNV-driven bias in Hi-C studies, which may deepen our understanding of changes in cancer 3D genome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87585 | GEO | 2017/11/17

SECONDARY ACCESSION(S): PRJNA345243

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Robust Hi-C maps of enhancer-promoter interactions reveal the function of non-coding genome in neural development and diseases

Project description:Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input “easy Hi-C” protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.

2020-07-31 | GSE116825 | GEO

Active chromatin and transcription play a key role in chromosome partitioning into topologiÑ?ally associating domains

Project description:Recent advances enabled by Hi-C technique have unraveled principles of chromosomal folding, which were since linked to many genomic processes. In particular, Hi-C revealed that chromosomes of animals are organized into Topologically Associating Domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. However, mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principals of TAD folding in Drosophila melanogaster, we performed Hi-C and PolyA+ RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e. the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predict TAD boundaries much worse than the active chromatin marks (in the minimal case, H3K4me3 and total RNA) do. Moreover, inter-TADs correspond to decompacted interbands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin that cannot be organized into compact structures, possibly due to high levels of histone acetylation. Finally, we test this hypothesis by polymer simulations, and find that TAD partitioning can be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin. Hi-C experiments, PolyA+ RNA profiling and mapping of chromosomal rearrangements in four Drosophila melanogaster cell lines.

2015-10-26 | E-GEOD-69013 | biostudies-arrayexpress

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

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

DeepLoop enables robust mapping of DNA loops from low-depth single cell or allele-resolved Hi-C data at high resolution

Project description:High-resolution mapping of the gene regulatory chromatin interactions from noisy Hi-C contact heatmaps remains a major challenge in 3D genome research due to the complex bias structure and severe data sparsity. Here we present DeepLoop, which addresses this problem by combining a rigorous bias correction strategy (HiCorr) and deep learning-based signal enhancement techniques. We demonstrated that DeepLoop can robustly identify high-resolution chromatin interactions from low-depth and single cell Hi-C data. With DeepLoop, we for the first-time mapped the genetic and epigenetic determinants of human homolog-specific chromatin loops in GM12878 cells at 5kb-resolution. We nominated two new imprinting loci with unbalanced DNA folding in additional to the well-known H19/IGF2 locus. Interestingly, we also found that the sub-TAD loops at the DXZ4 “megadomain” boundary escapes X-inactivation, but the loops at the FIRRE “superloop” locus do not escape. Unexpectedly, DeepLoop detected four previously unknown Mb-sized heterozygous structure variants in the GM12878 genome, including two large inversions causing allele-specific gene expression via enhancer rewiring. Finally, DeepLoop also pinpointed dozens of loop regulatory SNPs that often have transcriptional consequences. Taken together, DeepLoop expands the use of Hi-C to provide genome-wide insights into the genetics of 3D genome at loop resolution.

2022-03-14 | GSE167200 | GEO

The order and stochasticity in the Drosophila genome folding revealed by single-nucleus Hi-C

Project description:We generated and analyzed single-cell Hi-C libraries from cultrured Drosophila cells. The data obtained allowed us to explore cell-to-cell variability in TAD profiles and inter-TAD interactions showing that strong TAD boundaries are determined by high levels of active chromatin. DPD polymer simulations were utilized to reconstruct 3D structures of haploid X chromosomes. These structures showed marked cell-to-cell variabilty in the overall shape of the chromosome territory and relatively conserved chromatin chain path inside TADs. DPD polymer simulations were utilized to reconstruct 3D structures of haploid X chromosomes. These structures showed marked cell-to-cell variabilty in the overall shape of the chromosome territory and relatively conserved chromatin chain path inside TADs.

2020-10-22 | GSE131811 | GEO

Reorganization of 3D chromatin architecture in doxorubicin-resistant breast cancer cells

Project description:Doxorubicin resistance remains a major therapeutic challenge leading to treatment failure and poor survival prognosis in breast cancer. Although doxorubicin induces massive changes in the transcriptional landscape accompanied by alterations of chromatin accessibility are well known, potential diagnostic or therapeutic targets associated with three-dimensional (3D) genome reorganization in doxorubicin-resistant breast cancer cells have not yet been systematically investigated. Here we performed integrated analyses combining in situ high-throughput chromosome conformation capture (Hi-C), ATAC-seq and mHi-C data on doxorubicin-resistant MCF7 human breast cancer cells compared to parental cells. It revealed that A/B compartment switching was positively correlated to genome-wide differential gene expression, and the genome was spatially reorganized into smaller topologically associating domains (TADs) and loops. We also revealed the contribution of increased chromatin accessibility and potential transcription factor families, including CTCF and BORIS, to gained TAD boundaries and loop anchors. Intriguingly, we observed two condensed genomic regions (~20kb) with decreased chromatin accessibility flanking TAD boundaries, which might play a critical role in the formation or maintenance of TADs. Moreover, we identified a number of gained and lost enhancer-promoter interactions associated with differentially expressed genes, including FA2H, FOXA1, JRKL and EZH, some of which involved in chromatin organization and breast cancer signaling pathways. This study uncovered a close connection between 3D genome reorganization, chromatin accessibility as well as gene transcription, and provides resources and novel insights into the epigenomic mechanisms with potential therapeutic implications for doxorubicin resistance in breast cancer.

2022-06-14 | GSE205874 | GEO

Integrative Hi-C maps of pancreatic cancer

Project description:Pancreatic cancer's poor prognosis is caused by distal metastasis, which is associated with epigenomic changes. However, the roles of 3D epigenome in pancreatic cancer biology, especially its metastasis, remain unclear. Here we compare the 3D epigenomic and transcriptomic features among cells derived from pancreatic epithelial, primary and metastatic pancreatic cancer by integrated analysis of in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq data. We found A/B compartments, topologically associated domains (TADs), chromatin loops changed significantly in metastatic pancreatic cancer cells, which is associated with epigenetic state alterations. Moreover, we identified upregulated genes, which are located in switched compartments, common TADs with epigenetic state changing, specific TAD boundaries, and metastasis-specific enhancer-promoter loops, are related to cancer metastasis. We also find that the transcription factors mediated specific enhancer-promoter loops formation are also associated with metastasis. Taken together, these results provide a 3D epigenomic map of pancreatic cancer metastasis, which expands our knowledge of the epigenetic mechanism of pancreatic cancer metastasis and enables a better understanding of pancreatic cancer pathobiology.

2021-08-11 | GSE149103 | GEO

TCF-1 mediates 3D genome reconfiguration during T cell development (HiC)

Project description:Lineage-determine transcription factors (LDTFs) can determine gene expression programs of a specific cell type, by rewiring the linear regulatory network. However, it’s not clear whether and how LDTFs can alter the 3D genome organization during development. Here, we investigated the effect of T cell factor 1 (TCF-1) on the reconfiguration of 3D genome during T cell development. Topologically associated domains (TADs) that have higher density of TCF-1 gain more intra-TAD interactions during T cell development. TCF-1 colocalized with CCCTC-binding factor (CTCF) substantially reduced the insulation and increased the local interactions, which additionally have stronger interactions with T cell development genes. We further found that a considerable number of boundaries are lost during T cell development, and that TCF-1 is enriched at the lost boundaries, including the ones near key T cell development genes. Overexpression of TCF-1 in fibroblast demonstrates that both high density of TCF-1 and TCF-1 colocalized with CTCF can optimally increase the local interactions. Correspondingly, knocking out of TCF-1 in DN3 cell line leads to decreased intra-TAD interactions and gain of insulation at some of its binding sites. Finally, we found that TCF-1 can recruit and maintain cohesin at its binding sites, which probably cause reconfiguration of the 3D genome. Taken together, our study shows that TCF-1 can change the 3D genome at both TAD level and finer scale potentially through the recruitment of cohesin.

2022-02-24 | GSE178345 | GEO

TCF-1 mediates 3D genome reconfiguration during T cell development (ChIP-Seq)

2022-05-02 | GSE178346 | GEO