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Series GSE132426 Query DataSets for GSE132426
Status Public on Jun 11, 2019
Title Estrogen-independent molecular actions of mutant estrogen receptor alpha in endometrial cancer [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
 
Overall design ChIP-seq was used to study the effects of the D538G ESR1 mutation on genomic binding
 
Contributor(s) Blanchard Z, Gertz J
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Submission date Jun 10, 2019
Last update date Jun 13, 2019
Contact name Jason Gertz
E-mail(s) jay.gertz@hci.utah.edu
Organization name University of Utah
Department Oncological Sciences
Lab Gertz
Street address 2000 Circle of Hope
City Salt Lake CIty
State/province Utah
ZIP/Postal code 84112
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (22)
GSM3863225 WTClone1_Rep1_E2 (ChIP-seq)
GSM3863226 WTClone1_Rep1_DMSO (ChIP-seq)
GSM3863227 WTClone1_Rep2_E2 (ChIP-seq)
This SubSeries is part of SuperSeries:
GSE132430 Estrogen-independent molecular actions of mutant estrogen receptor alpha in endometrial cancer
Relations
BioProject PRJNA548067
SRA SRP200954

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
GSE132426_RAW.tar 3.4 Gb (http)(custom) TAR (of BEDGRAPH, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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