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Series GSE148277 Query DataSets for GSE148277
Status Public on Apr 08, 2020
Title Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and through secondary effects [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary While breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER’s actions, a significant number relapse. Approximately 30% of these recurrences harbor activating mutations in ER’s ligand binding domain. ER mutations have been shown to confer ligand-independent function to ER; however, much is still unclear regarding the effect of mutant ER beyond its estrogen independence. To investigate mutant ER’s molecular effects, we developed multiple isogenic ER mutant cell lines for the two most common ER ligand binding domain mutations, Y537S and D538G. We found that these mutations induce differential expression of thousands of genes, the majority of which are specific to one or the other mutation and are not observed upon estrogen treatment of wildtype cells. The mutant-specific genes show consistent differential expression across ER mutant lines developed in other laboratories. The observed gene expression changes cannot be explained by constitutive ER activity alone, as wildtype cells with long term estrogen exposure only exhibit some of these transcriptional changes, suggesting that mutant ER causes novel regulatory effects that are not simply due to constant activity. While ER mutations have minor effects on ER genomic binding, with the exception of ligand independence, we observed substantial differences in chromatin accessibility due to ER mutations. Mutant ER is bound to approximately a quarter of mutant-enriched accessible regions that are enriched for other DNA binding factors including FOXA1, CTCF, and OCT1. Our findings indicate that mutant ER causes several consistent effects on gene expression both indirectly and through constant activity.
 
Overall design ChIP-seq of ESR1 mutant and wildtype MCF-7 and T-47D breast cancer cell lines.
 
Contributor(s) Arnesen S, Gertz J
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Submission date Apr 07, 2020
Last update date Apr 10, 2020
Contact name Jason Gertz
E-mail(s) jay.gertz@hci.utah.edu
Organization name University of Utah
Lab Gertz
Street address 1950 Cir of Hope Dr
City Salt Lake City
State/province UT
ZIP/Postal code 84112
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (37)
GSM4459470 T47D_WT_clone1_DMSO_ChIPseq
GSM4459471 T47D_WT_clone2_DMSO_ChIPseq
GSM4459472 T47D_Y537S_clone1_DMSO_ChIPseq
This SubSeries is part of SuperSeries:
GSE148279 Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and through secondary effects
Relations
BioProject PRJNA623673
SRA SRP255669

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
GSE148277_RAW.tar 5.4 Gb (http)(custom) TAR (of BEDGRAPH, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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