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Series GSE51274 Query DataSets for GSE51274
Status Public on Apr 01, 2014
Title Breast tumor specific mutation in GATA3 impacts protein stability and genomic location
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-α (ERα)-positive breast tumors in which it participates with ERa and FOXA1 in a complex transcriptional regulatory program driving tumor growth. Paradoxically, GATA3 mutations are frequent in breast cancer and have been classified as drivers. To elucidate the contribution(s) of GATA3 alterations to oncogenesis, we studied two breast cancer cell lines, MCF7, which carries a heterozygous frameshift mutation in the second zinc finger of GATA3, and T47D, wild-type at this locus. Heterozygosity for the truncating mutation conferred protection from regulated turnover of GATA3, ERa and FOXA1 following estrogen stimulation. Thus, mutant GATA3 uncouples protein-level regulation of master regulatory transcription factors from hormone action. Consistent with increased protein stability, ChIP-seq profiling identified stronger accumulation of GATA3 in cells bearing the mutation, albeit with a similar distribution across the genome. We propose that this specific, cancer-derived mutation in GATA3 deregulates physiologic protein turnover, stabilizes GATA3 binding across the genome and modulates the response of mammary epithelial cells to hormone signaling, thus conferring a selective growth advantage.
Overall design Genome-wide mapping of GATA3 in two cell lines. There were two biological replicates and unchipped (input) DNA was used as reference.
Contributor(s) Adomas AB, Grimm SA, Malone C, Takaku M, Sims JK, Wade PA
Citation(s) 24758297
Submission date Sep 30, 2013
Last update date May 15, 2019
Contact name Paul A Wade
Phone 919-541-3392
Organization name NIEHS
Department Laboratory of Molecular Carcinogenesis
Street address 111 TW Alexander Drive
City Research Triangle Park
State/province NC
ZIP/Postal code 27709
Country USA
Platforms (1)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
Samples (8)
GSM1241752 MCF7 GATA3 rep1
GSM1241753 MCF7 input rep1
GSM1241754 T47D GATA3 rep1
BioProject PRJNA222284
SRA SRP030633

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Supplementary file Size Download File type/resource
GSE51274_MCF7.GATA3.bedGraph.gz 429.6 Mb (ftp)(http) BEDGRAPH
GSE51274_MCF7.GATA3.peaks.bed.gz 173.6 Kb (ftp)(http) BED
GSE51274_MCF7.input.bedGraph.gz 423.9 Mb (ftp)(http) BEDGRAPH
GSE51274_T47D.GATA3.bedGraph.gz 421.2 Mb (ftp)(http) BEDGRAPH
GSE51274_T47D.GATA3.peaks.bed.gz 96.5 Kb (ftp)(http) BED
GSE51274_T47D.input.bedGraph.gz 408.3 Mb (ftp)(http) BEDGRAPH
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