Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA341060 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4100160.fastq.gz | Fastqsanger.gz | |||
| SRR4100161.fastq.gz | Fastqsanger.gz | |||
| SRR4100153.fastq.gz | Fastqsanger.gz | |||
| SRR4100154.fastq.gz | Fastqsanger.gz | |||
| SRR4100155.fastq.gz | Fastqsanger.gz |
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Project description: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.
2017-02-13 | GSE86239 | GEO
Project description: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.
2017-02-13 | GSE86238 | GEO
Project description: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 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 can 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 reveal that the opposite function of ETS2 is a result of binding site competition and transcriptional attenuation due to weaker transcriptional activation by ETS2 compared to ETS1. This weaker activation was mapped to the ETS2 N-terminus and a specific interaction with the co-repressor ZMYND11 (BS69). Furthermore, ZMYND11 expression levels in patient tumors correlated with oncogenic versus 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.
| S-EPMC5416753 | biostudies-literature
Project description:Genome wide DNA binding of ETS1 and ETS2 in murine aortic endothelial cells
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Project description:This SuperSeries is composed of the SubSeries listed below.
2017-02-13 | GSE86240 | GEO
Project description:Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2
| PRJNA341062 | ENA
Project description:Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2
| PRJNA341061 | ENA
Project description:Angiogenesis is a highly orchestrated process involving complex crosstalk between several endothelial cell (EC) processes including cell cycle, cell survival and migration. Transcription factors ETS1 and ETS2 are required for EC functions necessary for embryonic angiogenesis. However owing to the lethal nature of the double mutant embryo, the specific gene targets of these factors are yet to be identified. In the current study, we try to elucidate the effect of endothelial cell specific deletion of Ets1 and Ets2 on post natal angiogenesis and characterize the downstream regulatory pathways. Deletion of Ets1 and Ets2, restricted to endothelial cells in new born mice (P1-P3), reduced retinal angiogenesis. Similarly, EC infiltration and invasion into matrigel plugs subsided when matrigel admixed with mouse mammary tumor cells was injected into adult mice with inactivated Ets1 and Ets2 specifically in ECs. Expression of key cell cycle and cell survival regulators were diminished in double mutant cells as compared to controls. In addition, both these factors were found to occupy the enhancer regions of the target genes. Deletion of Ets1 and Ets2 in cultured aortic EC resulted in altered cell cycle phases with a G2/M phase arrest and increased sensitivity to apoptosis in vitro. These results demonstrate that deletion of Ets1 and Ets2 in endothelial cells inhibits angiogenesis by altering cell cycle progression and decreasing cell survival.
2021-03-27 | GSE140157 | GEO
Project description:Angiogenesis is a highly orchestrated process involving complex crosstalk between several endothelial cell (EC) processes including cell cycle, cell survival and migration. Transcription factors ETS1 and ETS2 are required for EC functions necessary for embryonic angiogenesis. However owing to the lethal nature of the double mutant embryo, the specific gene targets of these factors are yet to be identified. In the current study, we try to elucidate the effect of endothelial cell specific deletion of Ets1 and Ets2 on post natal angiogenesis and characterize the downstream regulatory pathways. Deletion of Ets1 and Ets2, restricted to endothelial cells in new born mice (P1-P3), reduced retinal angiogenesis. Similarly, EC infiltration and invasion into matrigel plugs subsided when matrigel admixed with mouse mammary tumor cells was injected into adult mice with inactivated Ets1 and Ets2 specifically in ECs. Expression of key cell cycle and cell survival regulators were diminished in double mutant cells as compared to controls. In addition, both these factors were found to occupy the enhancer regions of the target genes. Deletion of Ets1 and Ets2 in cultured aortic EC resulted in altered cell cycle phases with a G2/M phase arrest and increased sensitivity to apoptosis in vitro. These results demonstrate that deletion of Ets1 and Ets2 in endothelial cells inhibits angiogenesis by altering cell cycle progression and decreasing cell survival.
2019-07-22 | GSE59744 | GEO