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| Status |
Public on Feb 13, 2017 |
| Title |
Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2 |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Aberrant activation of RAS/MAPK signaling is a driver of over one third of all human carcinomas. The homologous transcription factors ETS1 and ETS2 mediate the activation of gene expression programs downstream of RAS/MAPK signaling. ETS1 is important for oncogenesis in many tumor types. However, ETS2 can act as an oncogene in some cellular backgrounds, and as a tumor suppressor in others, and the molecular mechanism responsible for this cell-type specific function remains unknown. Here, we show that ETS1 and ETS2 regulate a cell migration gene expression program in opposite directions, and provide the first comparison of the ETS1 and ETS2 cistromes. This genomic data, and an ETS1 deletion line are used to show that the opposite function of ETS2 is due to binding site competition and a weaker activation function of ETS2 compared to ETS1. This weaker activation was mapped to the ETS2 N-terminus and a specific interaction with the co-repressor BS69 (ZMYND11). Gene expression data from tumor cohorts was then used to show that BS69 expression level in tumors correlates with oncogenic and tumor suppressive roles of ETS2. Therefore, these data indicate a novel and specific mechanism allowing ETS2 to switch between oncogenic and tumor suppressive functions in a cell-type specific manner.
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| |
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| Overall design |
ChIP-sequencing
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| |
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| Contributor(s) |
Plotnik JP, Hollenhorst PC |
| Citation(s) |
28119415 |
| Submission date |
Aug 30, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Josh Plotnik |
| E-mail(s) |
joshua.plotnik@abbvie.com
|
| Organization name |
AbbVie Inc.
|
| Street address |
1 North Waukegan Rd, AP10/210A
|
| City |
North Chicago |
| State/province |
IL |
| ZIP/Postal code |
60064 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE86240 |
Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2 |
|
| Relations |
| BioProject |
PRJNA341061 |
| SRA |
SRP083763 |
