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Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and through secondary effects

UID: 10767

Author(s): Gertz, Jason

Description
This superseries is composed of the subseries: GSE148276, GSE148277, and GSE148278.

Breast cancer patients with tumors that express estrogen receptor α (ER) at times harbor activating mutations in ER’s ligand binding domain. To investigate mutant ER’s molecular effects, multiple isogenic ER mutant cell lines for the two most common ER ligand binding domain mutations, Y537S and D538G, were developed. 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, substantial differences in chromatin accessibility due to ER mutations were noticed. 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. The findings indicate that mutant ER causes several consistent effects on gene expression both indirectly and through constant activity.
Subject of Study
Homo sapiens
Subject(s)
Breast Neoplasms
Estrogen Receptor alpha
Gene Expression
Receptors, Estrogen
OncoTree Cancer Type(s)
Breast
Access via GEO

Plain text, BEDGRAPH and NARROWPEAK files of expression profiling and genome binding/occupancy by high throughput sequencing
Accession #: GSE148279

Access via BioProject

Additional information about the overall initiative.
Accession #: PRJNA623670

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA and BioProject databases provide open access to these files. SRA and/or tar files can be downloaded directly from the site or viewed in the NCBI SRA Run Selector (link at bottom of page).
Associated Publications
Li F, Han M, Dai P, et al. Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide. Nature Communications. 2021; 12:866.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Software Used
SRA Toolkit

The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.

Dataset Format(s)
Plain Text, NARROWPEAK, BEDGRAPH
Data Tool(s)
RNA Seq
ChIP Seq
ATAC Seq
Dataset Size
6.7 GB
Data Catalog Record Updated
2021-07-26