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Deciphering the role of 3D genome organization in breast cancer susceptibility

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE184285 | GEO | 2022/01/11

REPOSITORIES: GEO

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Deciphering the Role of 3D Genome Organization in Breast Cancer Susceptibility.

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 the "Window of Susceptibility" (WOS). Rats have a similar WOS for developing breast cancer. A previous study in rat identified an age-specific long-range regulatory interaction for the cancer gene, Pappa, that is associated with breast cancer susceptibility. However, the global role of three-dimensional genome organization and downstream gene expression programs in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside the WOS. To systematically identify higher-order changes in 3D genome organization, we developed NE-MVNMF that combines network enhancement followed by multitask non-negative matrix factorization. We examined three-dimensional genome organization dynamics at the level of individual loops as well as higher-order domains. Differential chromatin interactions tend to be associated with differentially up-regulated genes with the WOS and recapitulate several human SNP-gene interactions associated with breast cancer susceptibility. Our approach identified genomic blocks of regions with greater overall differences in contact count between the two time points when the cluster assignments change and identified genes and pathways implicated in early carcinogenesis and cancer treatment. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may influence susceptibility to breast cancer.

| S-EPMC8787344 | biostudies-literature

Deciphering the role of 3D genome organization in breast cancer susceptibility (RNA-Seq)

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

Deciphering the role of 3D genome organization in breast cancer susceptibility (Hi-C)

2022-01-11 | GSE184280 | GEO

Deciphering the role of 3D genome organization in breast cancer susceptibility

Project description:Deciphering the role of 3D genome organization in breast cancer susceptibility

| PRJNA763885 | ENA

Deciphering the role of 3D genome organization in breast cancer susceptibility (RNA-Seq)

Project description:Deciphering the role of 3D genome organization in breast cancer susceptibility (RNA-Seq)

| PRJNA763890 | ENA

Deciphering the role of 3D genome organization in breast cancer susceptibility (Hi-C)

Project description:Deciphering the role of 3D genome organization in breast cancer susceptibility (Hi-C)

| PRJNA763891 | ENA

Anti-cancer drugs curaxins target the 3D genome organization

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-02-18 | GSE122463 | GEO

In vitro reconstitution of chromatin domains shows a role for nucleosome positioning in 3D genome organization

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-23 | GSE220647 | GEO

3D genome organization in the epithelial-mesenchymal transition spectrum

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-05-08 | GSE201919 | GEO

THE EPIGENOME PLAYS A MAJOR ROLE IN TOMATO 3D CHROMATIN ORGANIZATION

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-08-05 | GSE243911 | GEO

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