3D genome organization in the epithelial-mesenchymal transition spectrum [Hi-C]
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PROVIDER: PRJNA833402 | ENA |
REPOSITORIES: ENA
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Project description:3D genome organization in the epithelial-mesenchymal transition spectrum
| PRJNA833467 | ENA
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:3D genome organization in the epithelial-mesenchymal transition spectrum [scHi-C_OVCA429shGRHL]
| PRJNA833468 | ENA
Project description:3D genome organization in the epithelial-mesenchymal transition spectrum [scHi-C_PEO1HEYA8]
| PRJNA833470 | ENA
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 | GSE201918 | 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 | GSE201917 | GEO
Project description:Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are preferentially formed in regions containing high density of active genes and clusters of architectural protein binding sites. Transcription of most genes is turned off during the heat shock response in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. New heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies at the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be quickly reconfigured to allow new interactions between distant sequences. Analysis of 3D chromatin organization using Hi-C in Drosophila Kc167 cells. Cells were grown at 25 C and heat shocked for 20 min at 36.5 C. Cells were also treated with flavopiridol or triptolide to inhibit transcription elongation or initiation, respectively. Cells were depeleted of Cap-H2 or Rad21 using RNAi. Finally, cells depleted of RAd21 were subjected to heat shock at 36.5 C for 20 min.
2015-02-24 | E-GEOD-63515 | biostudies-arrayexpress
Project description:We investigate the spectrum of SVs and three-dimensional (3D) chromatin architecture in human pancreatic ductal epithelial cell carcinogenesis by using the state of art long-read single molecular real time (SMRT) and high-throughput chromosome conformation capture (Hi-C) sequencing techniques. Systematic integration of matched SMRT, in situ Hi-C, and RNA-seq datasets revealed the complicated dynamic interplay of SVs and 3D chromosome organization and their impacts on gene expression. Our studies identify and focus remodeling of chromatin folding domains associated with cross boundary SVs enabling aberrant interactions between regulatory elements. Moreover, our data also demonstrate the existence of complex genomic rearrangements associated with two key driver genes CDKN2A and SMAD4, and characterize their influence on cancer related gene expression from linear view to 3D perspective.
2022-05-01 | GSE185069 | GEO
Project description:Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines—Hep3B, Huh1, Huh7, and SNU449—using in situ Hi-C and ATAC-seq. Our findings revealed that HCCs had elevated long-range interactions compared to HMECs, both intra- and interchromosomal. Unexpectedly, they displayed cell line-specific compartmental modifications at the Mb scale, which could aid in determining HCC subtypes. At the sub-Mb scale, we observed a decrease in intra-TAD interactions and chromatin loops in HCCs compared to HMECs. Lastly, we discovered a correlation between gene expression and 3D chromatin architecture in SLC8A1, which encodes the sodium-calcium antiporter known to induce apoptosis. Our findings suggest that HCCs have a distinct 3D genome organization that is different from normal and other cancer cells. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will lead us to a better understanding of specific gene regulation mechanisms and uncover novel targets for cancer treatments.
2023-06-22 | GSE226216 | GEO
Project description:Triple-negative breast cancer (TNBC) is malignant cancer with a high risk of recurrence. To date, the underlying 3D chromatin organizations of TNBC have remained unclear. Here, using in situ Hi-C, we characterized the 3D chromatin organizations in cells representing five distinct subtypes of breast cancer (including TNBC) and TNBC tissues, compared to normal cells/tissues. We found that the global and local 3D architectures are severely disrupted in TNBC cells. Importantly, we detected CTCF-dependent TNBC-susceptible loss/gain of 3D chromatin organizations and found that these changes were strongly associated with perturbed chromatin accessibility and transcriptional dysregulations. Although some discrepancies exist between TNBC cell lines and tissues, we observed that perturbed local 3D architectures found in TNBC cells are partially conserved in TNBC tissues. Furthermore, we discovered distinct tissue-specific chromatin loops by comparing normal and TNBC tissues. Collectively, our findings provide important features of 3D chromatin organization in TNBC.
2022-05-06 | GSE167150 | GEO