FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditions
The selective expression of hypoxia‐inducible factor (HIF) target genes in different physiological and pathological environments forms the basis for cellular adaptation to hypoxia in development and disease. Several E26 transformation‐specific (ETS) transcription factors have been shown to specifica...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-08-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13220 |
| _version_ | 1797787929323503616 |
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| author | Guodan Zeng Tao Wang Jingyao Zhang Y. James Kang Li Feng |
| author_facet | Guodan Zeng Tao Wang Jingyao Zhang Y. James Kang Li Feng |
| author_sort | Guodan Zeng |
| collection | DOAJ |
| description | The selective expression of hypoxia‐inducible factor (HIF) target genes in different physiological and pathological environments forms the basis for cellular adaptation to hypoxia in development and disease. Several E26 transformation‐specific (ETS) transcription factors have been shown to specifically regulate the expression of a subset of HIF‐2 target genes. However, it is unknown whether there are ETS factors that specifically regulate hypoxia‐induced HIF‐1 target genes. The present study was undertaken to explore whether friend leukemia integration 1 (FLI1), an ETS transcription factor, regulates the expression of HIF‐1 target genes. To investigate this possibility, EA.hy926 cells were exposed to 20% O2 (normoxia) or 1% O2 (hypoxia). Western blotting, immunofluorescence staining, and RT‐qPCR revealed that FLI1 mRNA and protein levels increased slightly and that the FLI1 protein co‐localized with HIF‐1α in the nucleus under hypoxic conditions. Further analysis showed that, in the absence of FLI1, the hypoxia‐mediated induction of HIF‐1 target genes was selectively inhibited. The results from immunoprecipitation and luciferase reporter assays indicated that FLI1 cooperates with HIF‐1α and is required for the transcriptional activation of a subset of HIF‐1 target genes with a core promoter region containing FBS in proximity to a functional hypoxia response element (HRE). Furthermore, ChIP analysis further confirmed the direct interaction between FLI1 and the promoter region of FLI1‐dependent HIF‐1 target genes under hypoxia. Together, this study demonstrates that FLI1 is involved in the transactivation of certain HIF‐1 target genes in endothelial cells under hypoxic conditions. |
| first_indexed | 2024-03-13T01:28:24Z |
| format | Article |
| id | doaj.art-ac8000b0ceaf4e0785171525a22786a9 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-03-13T01:28:24Z |
| publishDate | 2021-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-ac8000b0ceaf4e0785171525a22786a92023-07-04T10:16:02ZengWileyFEBS Open Bio2211-54632021-08-011182174218510.1002/2211-5463.13220FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditionsGuodan Zeng0Tao Wang1Jingyao Zhang2Y. James Kang3Li Feng4Key Laboratory of Transplant Engineering and Immunology Ministry of Health West China Hospital Sichuan University Chengdu ChinaRegenerative Medicine Research Center West China Hospital Sichuan University Chengdu ChinaRegenerative Medicine Research Center West China Hospital Sichuan University Chengdu ChinaRegenerative Medicine Research Center West China Hospital Sichuan University Chengdu ChinaKey Laboratory of Transplant Engineering and Immunology Ministry of Health West China Hospital Sichuan University Chengdu ChinaThe selective expression of hypoxia‐inducible factor (HIF) target genes in different physiological and pathological environments forms the basis for cellular adaptation to hypoxia in development and disease. Several E26 transformation‐specific (ETS) transcription factors have been shown to specifically regulate the expression of a subset of HIF‐2 target genes. However, it is unknown whether there are ETS factors that specifically regulate hypoxia‐induced HIF‐1 target genes. The present study was undertaken to explore whether friend leukemia integration 1 (FLI1), an ETS transcription factor, regulates the expression of HIF‐1 target genes. To investigate this possibility, EA.hy926 cells were exposed to 20% O2 (normoxia) or 1% O2 (hypoxia). Western blotting, immunofluorescence staining, and RT‐qPCR revealed that FLI1 mRNA and protein levels increased slightly and that the FLI1 protein co‐localized with HIF‐1α in the nucleus under hypoxic conditions. Further analysis showed that, in the absence of FLI1, the hypoxia‐mediated induction of HIF‐1 target genes was selectively inhibited. The results from immunoprecipitation and luciferase reporter assays indicated that FLI1 cooperates with HIF‐1α and is required for the transcriptional activation of a subset of HIF‐1 target genes with a core promoter region containing FBS in proximity to a functional hypoxia response element (HRE). Furthermore, ChIP analysis further confirmed the direct interaction between FLI1 and the promoter region of FLI1‐dependent HIF‐1 target genes under hypoxia. Together, this study demonstrates that FLI1 is involved in the transactivation of certain HIF‐1 target genes in endothelial cells under hypoxic conditions.https://doi.org/10.1002/2211-5463.13220FLI1hypoxiahypoxia‐inducible factortranscription target gene |
| spellingShingle | Guodan Zeng Tao Wang Jingyao Zhang Y. James Kang Li Feng FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditions FEBS Open Bio FLI1 hypoxia hypoxia‐inducible factor transcription target gene |
| title | FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditions |
| title_full | FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditions |
| title_fullStr | FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditions |
| title_full_unstemmed | FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditions |
| title_short | FLI1 mediates the selective expression of hypoxia‐inducible factor 1 target genes in endothelial cells under hypoxic conditions |
| title_sort | fli1 mediates the selective expression of hypoxia inducible factor 1 target genes in endothelial cells under hypoxic conditions |
| topic | FLI1 hypoxia hypoxia‐inducible factor transcription target gene |
| url | https://doi.org/10.1002/2211-5463.13220 |
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