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Ets1 and Ets2 are required for endothelial cell survival during embryonic angiogenesis
Open accessAbstract
The ras/Raf/Mek/Erk pathway plays a central role in coordinating endothelial cell activities during angiogenesis. Transcription factors Ets1 and Ets2 are targets of ras/Erk signaling pathways that have been implicated in endothelial cell function in vitro, but their precise role in vascular formation and function in vivo remains ill-defined. In this work, mutation of both Ets1 and Ets2 resulted in embryonic lethality at midgestation, with striking defects in vascular branching having been observed. The action of these factors was endothelial cell autonomous as demonstrated using Cre/loxP technology. Analysis of Ets1/Ets2 target genes in isolated embryonic endothelial cells demonstrated down-regulation of Mmp9, Bcl-XL, and cIAP2 in double mutants versus controls, and chromatin immunoprecipitation revealed that both Ets1 and Ets2 were loaded at target promoters. Consistent with these observations, endothelial cell apoptosis was significantly increased both in vivo and in vitro when both Ets1 and Ets2 were mutated. These results establish essential and overlapping functions for Ets1 and Ets2 in coordinating endothelial cell functions with survival during embryonic angiogenesis.
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“Genes possibly repressed by SOX9 include endothelial markers, such as VWF and PECAM1, as well as genes encoding TFs important for endothelial cell functions, including ERG (60) and ETS2 (61).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [61]
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“F or p er so na l u se o nl y. H1 S1 S2 H2 H3 S3 S4 H4 H5HI-2HI-1 H0 H1 H2 H3 H4 H5H2' ETS domain ** ETS1, ETS2 GABPA, ETV6 ELK4 FLI1, SPI1, SPDEF, ELF3, ELF5, ELK1 ERG, FLI1, ETV6, Yan GABPA, SPDEF ETS1, ETS2, Pnt-P2 PNT domain SAM domain H1 S1 S2 H2 H3 S3 S4 H4 H5 HI-2 HI-1 H0 H1 H2 H3 H4 H5 H2' * * a b SRR N PNT C…”
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Self-citation
Metadata
- Authors
- Wei, G., Srinivasan, R., Cantemir-Stone, C. Z., Sharma, S. M., Santhanam, R., Weinstein, M., Muthusamy, N., Man, A. K., Oshima, R. G., Leone, G., & Ostrowski, M. C.
- Affiliations
- Department of Molecular and Cellular Biochemistry,
- The Comprehensive Cancer Center,
- The Ohio State University (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-07-30
- Volume
- 114
- Issue
- 5
- Pages
- 1123-1130
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2721789
- OpenAlex
- W2067611733
- Cited by
- 185
- References
- 46
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 14 · 2023: 13 · 2022: 14 · 2021: 7 · 2020: 12 · 2019: 4 · 2018: 2 · 2017: 12 · 2016: 12 · 2015: 11 · 2014: 5 · 2013: 17 · 2012: 8
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ohio State University
- National Cancer Institute (R01CA053271, P01CA097189, R01-CA53271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- ETS1, ETS2, endothelial cell survival, embryonic angiogenesis, endothelial cell apoptosis, vascular branching, MMP-9, Bcl-xL, cIAP2, Ras/ERK signaling
- MeSH terms
- Animals, Blood Vessels, Cell Survival, Chimera, Edema, Embryo Transfer, Fetal Death, Fetal Diseases, Genetic Vectors, Hemorrhage, Homozygote, Phenotype, Apoptosis, Mice, Knockout, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, Endothelial Cells, Embryonic Development, Proto-Oncogene Protein c-ets-1, Proto-Oncogene Protein c-ets-2, Mice
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