Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global mapping of estrogen receptor and histone modifications in breast tumor samples uncovers distinct patterns for aromatase inhibitor resistance

ABSTRACT: ChIP-seq on primary breast cancer tumor samples for Era, H3K4me3, H3K27me3. Patients had a poor or good outcome after aromatase inhibitor treatment. Differential binding patterns between good and poor outcome patients were identified for each marker, predicting response to treatment comparing ER, H3K4me3 and H3K27me3 patterns between two breast cancer patient populations

ORGANISM(S): Homo sapiens

SUBMITTER: Wilbert Zwart

PROVIDER: E-GEOD-40867 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Hallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancer.

Jansen Maurice P H M MP Knijnenburg Theo T Reijm Esther A EA Simon Iris I Kerkhoven Ron R Droog Marjolein M Velds Arno A van Laere Steven S Dirix Luc L Alexi Xanthippi X Foekens John A JA Wessels Lodewyk L Linn Sabine C SC Berns Els M J J EM Zwart Wilbert W

Cancer research 20131101 22

Aromatase inhibitors are the major first-line treatment of estrogen receptor-positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor α (ERα), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ...[more]

PMID: 24242068

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Project description:The ability of cells to perceive and translate versatile cues into differential chromatin and transcriptional states is critical for many biological processes1-4. In plants, timely transition to a flowering state is crucial for successful reproduction5-7. EARLY BOLTING IN SHORT DAY (EBS) is a negative transcriptional regulator that prevents premature flowering in Arabidopsis8,9. Here, we revealed that bivalent bromo-adjacent homology (BAH)-plant homeodomain (PHD) reader modules of EBS bind H3K27me3 and H3K4me3, respectively. A subset of EBS-associated genes was co-enriched with H3K4me3, H3K27me3, and the Polycomb repressor complex 2 (PRC2). Interestingly, EBS adopts an auto-inhibition mode to mediate its binding preference switch between H3K27me3 and H3K4me3. This binding balance is critical because disruption of either EBS-H3K27me3 or EBS-H3K4me3 interaction induces EBS-mediated early floral transition. This study identifies a single bivalent chromatin reader capable of recognizing two antagonistic histone marks and reveals a distinct mechanism of interplay between active and repressive chromatin states.The ability of cells to perceive and translate versatile cues into differential chromatin and transcriptional states is critical for many biological processes1-4. In plants, timely transition to a flowering state is crucial for successful reproduction5-7. EARLY BOLTING IN SHORT DAY (EBS) is a negative transcriptional regulator that prevents premature flowering in Arabidopsis8,9. Here, we revealed that bivalent bromo-adjacent homology (BAH)-plant homeodomain (PHD) reader modules of EBS bind H3K27me3 and H3K4me3, respectively. A subset of EBS-associated genes was co-enriched with H3K4me3, H3K27me3, and the Polycomb repressor complex 2 (PRC2). Interestingly, EBS adopts an auto-inhibition mode to mediate its binding preference switch between H3K27me3 and H3K4me3. This binding balance is critical because disruption of either EBS-H3K27me3 or EBS-H3K4me3 interaction induces EBS-mediated early floral transition. This study identifies a single bivalent chromatin reader capable of recognizing two antagonistic histone marks and reveals a distinct mechanism of interplay between active and repressive chromatin states.v

Dataset Information

Global mapping of estrogen receptor and histone modifications in breast tumor samples uncovers distinct patterns for aromatase inhibitor resistance

Publications

Hallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancer.

Similar Datasets

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