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Series GSE86239 Query DataSets for GSE86239
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 Expression 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.
Overall design mRNA profiles of ETS2 knockdown DU145 cells were generated using deep sequencing, in triplicate, using Illumina NextSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.

This series includes re-analysis of three luciferase shRNA samples from GSE59020.
Contributor(s) Plotnik JP, Hollenhorst PC
Citation(s) 28119415
Submission date Aug 30, 2016
Last update date May 15, 2019
Contact name Josh Plotnik
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 (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (6)
GSM2298953 ETS2 knockdown in DU145 cells using shRNA replicate 1
GSM2298954 ETS2 knockdown in DU145 cells using shRNA replicate 2
GSM2298955 ETS2 knockdown in DU145 cells using shRNA replicate 3
This SubSeries is part of SuperSeries:
GSE86240 Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2
BioProject PRJNA341062
SRA SRP083762

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE86239_ETS2shRNA_gene_exp.diff.gz 703.0 Kb (ftp)(http) DIFF
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Raw data are available in SRA
Processed data are available on Series record

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