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Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine resistant breast cancer

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE118716 | GEO | 2019/12/11

REPOSITORIES: GEO

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Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer.

Project description:Endocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer.

| S-EPMC6965612 | biostudies-literature

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [WGBS]

Project description:Endocrine therapy resistance invariably develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine resistant breast cancer cells and that the differential interactions are enriched for genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. Importantly, new 3D chromatin interactions often occur coincidently with hypermethylation and loss of ER binding. Additionally, alterations in active (A-type) and inactive (B-type) chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer.

2019-12-11 | GSE118714 | GEO

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [WGS]

2019-12-11 | GSE118715 | GEO

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [ChIP-seq]

2019-12-11 | GSE118711 | GEO

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [RNA-seq]

2019-12-11 | GSE118713 | GEO

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [Hi-C]

2019-12-11 | GSE118712 | GEO

Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine resistant breast cancer

Project description:Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine resistant breast cancer

| PRJNA486524 | ENA

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [WGS]

Project description:Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [WGS]

| PRJNA486532 | ENA

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [WGBS]

Project description:Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [WGBS]

| PRJNA486530 | ENA

Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [RNA-seq]

Project description:Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [RNA-seq]

| PRJNA486526 | ENA

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