Hi-C profiling in tissues reveals 3D chromatin-regulated breast tumor heterogeneity informing a looping-mediated therapeutic avenue
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1085994 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28279770_1.fastq.gz | Fastqsanger.gz | |||
| SRR28279770_2.fastq.gz | Fastqsanger.gz | |||
| SRR28279771_1.fastq.gz | Fastqsanger.gz | |||
| SRR28279771_2.fastq.gz | Fastqsanger.gz | |||
| SRR28279772_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Current knowledge in three-dimensional (3D) chromatin regulation in normal and disease states was mostly accumulated through Hi-C profiling in in vitro cell culture system. The limitations include failing to recapitulate disease-specific physiological properties and often lacking clinically relevant disease microenvironment. In this study, we conduct tissue-specific Hi-C profiling in a pilot cohort of 12 breast tissues comprising of two normal tissues (NTs) and ten ER+ breast tumor tissues (TTs) including five primary tumors (PTs), and five tamoxifen-treated recurrent tumors (RTs). We find largely preserved compartments, highly heterogeneous topological associated domains (TADs) and intensively variable chromatin loops among breast tumors, demonstrating 3D chromatin-regulated breast tumor heterogeneity. Further cross-examination identifies RT-specific looping-mediated biological pathways and suggests CA2, an enhancer-promoter looping (EPL)-mediated target gene within the bicarbonate transport metabolism pathway, might play a role in driving the tamoxifen resistance. Remarkably, the inhibition of CA2 not only impedes tumor growth both in vitro and in vivo, but also reverses chromatin looping. Our study thus yields significant mechanistic insights into the role and clinical relevance of 3D chromatin architecture in breast cancer endocrine resistance.
2025-03-03 | GSE261230 | GEO
Project description:Organoids or spheroids have emerged as a physiologically relevant in vitro preclinical model to study patient-specific diseases. A recent study used spheroids of MCF10 cells to model breast cancer progression and identified targetable alterations more similar to those in vivo. Thus, it is practical and essential to explore and characterize the spheroids of the commonly used human breast cancer (BC) cells. This study conducted Hi-C analyses in three-dimensional (3D) spheroids of MCF10A, MCF7 and MCF7TR cells and compared TADs and looping genes with those in 2D monolayers. We found that chromatin domains and looping genes’ strength have drastically changed during the 3D culture growth, although we identified very similar numbers of TADs and looping genes. We further identified novel 3D growth-specific looping genes within Hippo relevant pathways, of which two genes showed potential prognostic values in measuring the outcome of the endocrine treatment. We finally confirmed a few selected Hippo relevant pathways genes with enhanced looping in breast cancer patient tissues’ organoid. Hence, our work has provided significant insights into our understanding of 3D-growth-specific chromatin architecture in tamoxifen-resistant breast cancer.
2021-09-29 | GSE165570 | GEO
Project description:Recent advances in high-throughput transcriptomics have revealed extensive gene expression changes during cerebral ischemia. However, the changes in 3D chromatin architecture and long-range chromatin looping between genes and distal regulatory elements that drive these gene expression changes remain virtually unexplored. In this study, we mapped the landscape of altered 3D chromatin looping the in the ischemic cortex and evaluated its contributions to post-stroke transcriptional changes. We used genome-wide chromatin conformation capture (Hi-C) to profile changes in the 3D chromatin architecture in the cerebral cortex of adult mice following a 1 h middle cerebral artery occlusion and 6 h of reperfusion, or sham surgery. We identified a total of 15,592 loops in the stroke group with a mean enrichment core of 6.108, and these included 1973 promoter-promoter contacts, 7857 enhancer-enhancer contacts, and 5762 enhancer-promoter contacts. In the sham group, there were 14,779 chromatin loops with a mean enrichment score of 5.473, including 1714 promoter-promoter contacts, 8597 enhancer-enhancer contacts, and 4468 enhancer-promoter contacts. Together, our study represents the first genome-wide evaluation of 3D chromatin looping following stroke.
2025-05-30 | GSE294767 | GEO
Project description:Organoids or spheroids have emerged as a physiologically relevant in vitro preclinical model to study patient-specific diseases. A recent study used spheroids of MCF10 cells to model breast cancer progression and identified targetable alterations more similar to those in vivo. Thus, it is practical and essential to explore and characterize the spheroids of the commonly used human breast cancer (BC) cells. This study conducted Hi-C analyses in three-dimensional (3D) spheroids of MCF10A, MCF7 and MCF7TR cells and compared TADs and looping genes with those in 2D monolayers. We found that chromatin domains and looping genes’ strength have drastically changed during the 3D culture growth, although we identified very similar numbers of TADs and looping genes. We further identified novel 3D growth-specific looping genes within Hippo relevant pathways, of which two genes showed potential prognostic values in measuring the outcome of the endocrine treatment. We finally confirmed a few selected Hippo relevant pathways genes with enhanced looping in breast cancer patient tissues’ organoid. Hence, our work has provided significant insights into our understanding of 3D-growth-specific chromatin architecture in tamoxifen-resistant breast cancer.
2021-09-29 | GSE165571 | GEO
Project description:Although the Hi-C maps in cultured immune cell has been reported, there still lacks 3D landscape of human primary monocytes. The peripheral blood from two health people and two SLE patients was collected and CD14+ monocytes were selected to perform Hi-C, RNA-seq, ATAC-seq and ChIP-seq. The raw data of THP1 cell Hi-C library was also used in comparison. We firstly presented the 3D genome structure heterogeneity in human primary monocytes. Significantly diversity of chromatin interaction in HLA complex region might regulates many immunologic processes. The chromatin loop regulation around CD16 and its relevant expression pattern indicated the CD16 associated monocyte functions are dominated regulated by this variable TAD boundary.
2022-01-01 | GSE157971 | GEO
Project description:The transcription factor ZNF143 contains seven tandem zinc fingers and is involved in 3D genome construction; however, the mechanism by which ZNF143 functions in chromatin looping remains unclear. Here, we show that ZNF143 directionally recognizes diverse genomic sites and is required for chromatin looping between these sites. In addition, ZNF143 is located between CTCF and cohesin at numerous CTCF sites and ZNF143 removal narrows the space between CTCF and cohesin. Moreover, genetic deletion of ZNF143, in conjunction with acute CTCF depletion, revealed that ZNF143 and CTCF collaborate to regulate higher-order genome organization. Thus, ZNF143 is recruited by CTCF to the CTCF sites to regulate TAD formation and genome compartmentalization whereas directional recognition of DNA motifs directly by ZNF143 itself regulates promoter activity via chromatin looping.
2023-11-07 | GSE236634 | GEO
Project description:Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as a “Window of Susceptibility” (WOS). Radiation exposures poses a high breast cancer risk for women between the early childhood and young adult stage and is reduced in the mid-30s. Rats have a similar WOS for developing breast cancer. Previous studies have identified a looping interaction between a genomic region in the mammary carcinoma susceptibility Mcs5c locus and a known cancer gene, PAPPA. However, the global role of three-dimensional organization in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside WOS. We compared the temporal changes in chromosomal looping to those in expression and find that interactions that have significantly higher counts within WOS are significantly enriched for genes upregulated in WOS. To systematically identify higher-order changes in 3D genome organization, we developed an approach that combines network enhancement to smooth the Hi-C matrices followed by multitask non-negative matrix factorization (NMF) to identify clusters of interacting loci. We found that large-scale topological re-organizations are enriched for differential interactions within and outside the WOS timepoints. Finally, we mapped previously published breast-cancer associated human GWAS variants to rat loci and identified the corresponding rat ortholog gene interacting with the loci. Many of the associated rat genes participate in differential interactions, recapitulate the human SNP- gene interactions and are associated with breast cancer. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may increase susceptibility to breast cancer.
2022-01-11 | GSE184280 | GEO
Project description:Background The plasticity along the epithelial-mesenchymal transition (EMT) spectrum has been shown to be regulated by various epigenetic repertoires. Emerging evidence of local chromatin conformation changes suggests that regulation of EMT may occur at a higher order of three-dimensional genome level. Results We perform Hi-C analysis and combine ChIP-seq data across cancer cell lines representing different EMT states. We demonstrate that the epithelial and mesenchymal genes are regulated distinctively. We find that EMT genes are regulated within their topologically associated domains (TADs), with only a subset of mesenchymal genes being influenced by A/B compartment switches, indicating topological remodelling is required in the transcriptional regulation of these genes. At the TAD level, epithelial and mesenchymal genes are associated with different regulatory trajectories. The epithelial gene-residing TADs are enriched with H3K27me3 marks in the mesenchymal-like states. The mesenchymal gene-residing TADs , which do not show enrichment of H3K27me3 in epithelial-like states, exhibit increased interaction frequencies with regulatory elements in the mesenchymal-like states. Conclusions We propose a novel workflow coupling immunofluorescence and dielectrophoresis to unravel EMT heterogeneity at single-cell resolution. The predicted three-dimensional structures of chromosome 10, harboring Vimentin, identify cell clusters of different states. Our results pioneer a novel avenue to decipher the complexities underlying the regulation of EMT and may infer the barriers of plasticity in the 3D genome context.
2022-05-08 | GSE201878 | GEO
Project description:Comparative 3D Genome Architecture in Vertebrates (Hi-C)
| PRJNA704984 | ENA
Project description:The chromatins are folded into three-dimensional (3D) structures, and aberrant chromatin 3D folding has been shown in cancer. We performed ATAC-seq and TOP2A ChIP-seq to profile the potential effects of different anthracyclines on the chromatin. We identified that unique anthracycline variants selectively target chromatin looping anchors via disrupting CTCF binding, suggesting an additional potential therapeutic effect on the 3D genome. We further performed Hi-C experiments, and data from K562 cells treated with the selective anthracycline drugs indicate that the global 3D chromatin organizations were disrupted dramatically, as exemplified by the disruption of distal regulation of the Myc gene. Furthermore, AML patients receiving anthracycline drugs showed altered chromatin structures around potential looping anchors, which linked to distinct clinical outcomes. Our data indicate that anthracyclines are potent and selective epigenomic targeting drugs and can further target the 3D genome for anticancer effects, which could be explored for personalized medicine to treat tumors with aberrant 3D chromatin structures.
2025-01-14 | GSE285987 | GEO