Deciphering the role of 3D genome organization in breast cancer susceptibility (Hi-C)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA763891 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15914064_1.fastq.gz | Fastqsanger.gz | |||
| SRR15914064_2.fastq.gz | Fastqsanger.gz | |||
| SRR15914065_1.fastq.gz | Fastqsanger.gz | |||
| SRR15914065_2.fastq.gz | Fastqsanger.gz | |||
| SRR15914066_1.fastq.gz | Fastqsanger.gz |
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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:Deciphering the role of 3D genome organization in breast cancer susceptibility
| PRJNA763885 | ENA
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 | GSE184284 | GEO
Project description:Deciphering the role of 3D genome organization in breast cancer susceptibility (RNA-Seq)
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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:3D genome organization in the epithelial-mesenchymal transition spectrum [Hi-C]
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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
Project description:Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers [Hi-C]
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Project description:Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma [Hi-C]
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