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Series GSE244840 Query DataSets for GSE244840
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
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.
 
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
Submission date Oct 06, 2023
Last update date Jun 03, 2024
Contact name Wilbert Zwart
E-mail(s) w.zwart@nki.nl
Organization name Netherlands Cancer Institute
Department Oncogenomics
Lab Zwart lab
Street address Plesmanlaan 121
City Amsterdam
State/province Noord-Holland
ZIP/Postal code 1066CX
Country Netherlands
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (5)
GSM7830649 ERa_BRCa_patient_1
GSM7830650 ERa_BRCa_patient_2
GSM7830651 ERa_BRCa_patient_3
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
Relations
BioProject PRJNA1024995

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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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