Homo sapiens
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR101429.fastq.gz | Fastqsanger.gz | |||
| DRR101430.fastq.gz | Fastqsanger.gz | |||
| DRR101431.fastq.gz | Fastqsanger.gz | |||
| DRR101432.fastq.gz | Fastqsanger.gz | |||
| DRR101433.fastq.gz | Fastqsanger.gz |
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Project description:Elucidation of the genome-wide chromatin interactions for therapy-resistance of ER positive breast cancer
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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 | GSE118715 | GEO
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 | GSE118711 | GEO
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
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 | GSE118713 | GEO
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 | GSE118712 | GEO
Project description:Hormone therapy targeting estrogen receptor (ER) is the principal treatment for ER-positive breast cancers but many cancers develop resistance to anti-estrogens. Cyclin-dependent kinase 8 (CDK8) is a transcriptional regulator of several oncogenic pathways. Expression levels of CDK8 and ERα are inversely correlated in breast cancers suggesting a functional association between CDK8 and ER. CDK8 inhibition by selective small-molecule inhibitors, by shRNA knockdown or by CRISPR-Cas9 knockout suppressed estrogen-induced transcription, with no significant effects on ERα protein expression or phosphorylation. CDK8 inhibition also abrogated the mitogenic effect of estrogen on ER-positive breast cancer cells and potentiated growth inhibition by the ER antagonist fulvestrant. In vivo, administration of a CDK8 inhibitor suppressed ER-positive breast cancer xenograft growth and augmented the effects of fulvestrant with no apparent toxicity. CDK8 inhibitors also suppressed the development of estrogen independence in ER-positive breast cancer cells. These results identify CDK8 as a novel drug target for breast cancer therapy.
2017-02-14 | GSE93193 | GEO
Project description:Around 35% of Estrogen Receptor (ER) positive patients develop resistance and relapse, highlighting the need to further understand the mechanisms underpinning endocrine resistance in breast cancer. Here, we study 3-dimensional (3D) epigenome remodelling in endocrine resistant breast cancer cells. We show that chromatin interactions both within and between topologically associating domains (TADs) frequently change in resistant breast cancer cells and that alterations in active (A-type) and inactive (B-type) chromosomal compartments are associated with decreased ER binding and atypical interactions and gene expression. Finally, we identify differentially interacting ER-bound regions that preferentially connect active enhancers and promoters associated with altered expression of ER-regulated genes. Importantly, interactions specifically associated with endocrine resistance, often occur coincidently with hypermethylation of ER binding. Our results demonstrate that 3D epigenome remodelling is a key mechanism of endocrine resistance that consists of differential chromatin interactions and aberrant DNA methylation at ER-regulated enhancer regions.
2019-12-11 | GSE130916 | GEO
Project description:Endocrine therapy resistance is a clinical problem for the management of estrogen receptor (ER)-positive breast cancer. The elucidation of factors that modulate ER signaling will provide useful information for understanding the pathophysiology of ER-positive and endocrine-resistant breast cancers. In the screen of estrogen-inducible lncRNAs transcribed from ER alpha-associated active promoters/enhancers, a novel estrogen-inducible lncRNA BNAT1 (breast cancer natural antisense transcript 1), which is transcribed from the proximal promoter region of COL18A1, was identified in ER+ MCF7 cells. siRNA-mediated BNAT1 silencing significantly inhibited the in vitro and in vivo growth of tamoxifen-resistant MCF7 cells.To examine the role of long non-coding RNA BNAT1 (alias gene name COL18AS was used in this dataset) in ER+ breast cancer, MCF7 cells were treated with siRNAs targeting BNAT1 (siCOL18AS, or siBNAT1) or control siRNA (siCtrl, or siControl). The microarray study showed that BNAT1 was closely associated with estrogen signaling pathway.
2025-08-31 | GSE212683 | GEO
Project description:Phenotypic plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced phenotypic plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies, including GRO-seq on enhancer landscapes, demonstrate that the global enhancer gain/loss reprogramming driven by the differential interactions between ER-alpha and other oncogenic transcription factors (TFs), predominantly GATA3 and AP1, profoundly alters breast cancer transcriptional programs. Our functional studies in multiple biological systems support a coordinate role of GATA3 and AP1 in enhancer reprogramming that drives phenotypic plasticity to achieve endocrine resistance or cancer invasive progression. Thus, changes in TF-TF and TF-enhancer interactions can lead to genome-wide enhancer reprogramming, resulting in transcriptional dysregulations that promote plasticity and cancer therapy-resistance progression
| MSV000083857 | MassIVE