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| Status |
Public on Mar 27, 2024 |
| Title |
Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Estrogen Receptor 1 (ESR1; also known as ERα, encoded by ESR1 gene) is the main driver and prime drug target in luminal breast cancer. ESR1 chromatin binding is extensively studied in cell lines and a limited number of human tumors, using consensi of peaks shared among samples. However, little is known about inter-tumor heterogeneity of ESR1 chromatin action, along with its biological implications. Here, we use a large set of ESR1 ChIP-seq data from 70 ESR1+ breast cancers to explore inter-patient heterogeneity in ESR1 DNA binding to reveal a striking inter-tumor heterogeneity of ESR1 action. Of note, commonly shared ESR1 sites show the highest estrogen-driven enhancer activity and are most engaged in long-range chromatin interactions. In addition, the most commonly shared ESR1-occupied enhancers are enriched for breast cancer risk SNP loci. We experimentally confirm SNVs to impact chromatin binding potential for ESR1 and its pioneer factor FOXA1. Finally, in the TCGA breast cancer cohort, we can confirm these variations to associate with differences in expression for the target gene. Cumulatively, we reveal a natural hierarchy of ESR1–chromatin interactions in breast cancers within a highly heterogeneous inter-tumor ESR1 landscape, with the most common shared regions being most active and affected by germline functional risk SNPs for breast cancer development.
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| Overall design |
Estrogen receptor alpha ChIP-seq (ERa, SX-543, Santa Cruz) has been performed on 5 female primary breast tumor tissues. Raw data are available with restricted access at the EGA under accession number EGAS50000000008.
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Submitter states that missing raw files are due to patient privacy concerns.
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| Contributor(s) |
Joosten SE, Gregoricchio S, Stelloo S, Yapıcı E, Huang CF, Donaldson Collier M, Morova T, Altintas U, Kim Y, Canisius S, Korkmaz G, Lack NA, Vermeulen M, Linn SC, Zwart W |
| Citation(s) |
38719469 |
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| Submission date |
Oct 06, 2023 |
| Last update date |
Jun 03, 2024 |
| Contact name |
Wilbert Zwart |
| E-mail(s) |
w.zwart@nki.nl
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| Organization name |
Netherlands Cancer Institute
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| Department |
Oncogenomics
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| Lab |
Hormone-dependent cancers
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| Street address |
Plesmanlaan 121
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| City |
Amsterdam |
| State/province |
Noord-Holland |
| ZIP/Postal code |
1066CX |
| Country |
Netherlands |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE244845 |
Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions |
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| Relations |
| BioProject |
PRJNA1024995 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE244840_RAW.tar |
640.5 Mb |
(http)(custom) |
TAR (of BED, BW) |
| Raw data not provided for this record |
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