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| Status |
Public on Feb 27, 2020 |
| Title |
GATA3 mutation disrupts functional network governed by Estrogen receptor, FOXA1 and GATA3 |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Estrogen Receptor (ER) is a steroid hormone receptor that regulates epithelial genes in breast cancer. ER forms a regulatory network with the other transcription factors, FOXA1 and GATA3. GATA3 is known to be capable of specifying chromatin localization of FOXA1 and ER. GATA3 has been identified as one of the most frequently mutated genes in breast cancer. However, how GATA3 mutations impact this transcriptional network is unknown. Here we investigate the function of one of the recurrent patient-derived GATA3 mutations (R330fs) for this regulatory network. Genomic analysis indicates that the R330fs mutant can disrupt the cooperative action of ER, FOXA1, and GATA3, and induce chromatin relocalization of these factors. Relocalizations of ER and FOXA1 are associated with altered chromatin architectures leading to differential gene expression in the GATA3 mutant cells. These results suggest the active role of GATA3 mutants in ER positive breast tumors.
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| |
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| Overall design |
Genome-wide mapping of chromatin architectures in GATA3 mutant T47D cells
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| |
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| Contributor(s) |
Takaku M, Grimm SA, Paul WA |
| Citation(s) |
32232341 |
| |
| Submission date |
May 03, 2019 |
| Last update date |
May 26, 2020 |
| Contact name |
Paul A Wade |
| E-mail(s) |
[email protected]
|
| 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 |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA541008 |
| SRA |
SRP194971 |
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