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| Status |
Public on Jun 12, 2019 |
| Title |
Cistromic re-programming by truncating GATA3 mutations promotes mesenchymal transformation in vitro, but not mammary tumour formation in mice [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Heterozygous mutations in the transcription factor GATA3 are identified in 10-15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expression and promotes anchorage-independent growth in vitro. However, we could not identify any effects of truncated GATA3 expression on mammary gland development or mammary tumor formation in mice. Together, our results demonstrate that both truncated GATA3 mutants promote cistromic re-programming of GATA3 in vitro, but these mutants are not sufficient to induce tumor formation in mice.
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| Overall design |
Binding of HA-tagged wild-type GATA3 (HA_GATA3_wt) and two truncated variants (HA_GATA3_TR1 and HA_GATA3_TR2) exogenously introduced in T47D cells profiled by ChIP-seq (Chromatin Immunoprecipitation followed by deep sequencing).
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| Contributor(s) |
Cornelissen LM, de Bruijn R, Henneman L, Kim Y, Zwart W, Jonkers J |
| Citation(s) |
31218575 |
| |
| Submission date |
Nov 23, 2018 |
| Last update date |
Jun 21, 2019 |
| Contact name |
Lisette Cornelissen |
| E-mail(s) |
l.cornelissen@nki.nl
|
| Organization name |
The Netherlands Cancer Institute
|
| Street address |
Plesmanlaan 121
|
| City |
Amsterdam |
| ZIP/Postal code |
1066 CX |
| Country |
Netherlands |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (26)
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| This SubSeries is part of SuperSeries: |
| GSE122849 |
Cistromic re-programming by truncating GATA3 mutations promotes mesenchymal transformation in vitro, but not mammary tumour formation in mice |
|
| Relations |
| BioProject |
PRJNA506682 |
| SRA |
SRP170414 |
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