GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis
Summary: Endometrial angiogenesis is necessary for good endometrial receptivity. Krüppel-like factor 4 (KLF4) is a transcription factor that is essential for regulating angiogenesis. Here we found that vascular endothelial growth factor A (VEGFA) can form a positive feedback loop with KLF4 to promot...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-07-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222007805 |
| _version_ | 1828815211495161856 |
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| author | Can Cao Yuling Zhou Yu Zhang Yucong Ma Shujin Du Lijie Fan Ruobing Niu Yingmei Zhang Ming He |
| author_facet | Can Cao Yuling Zhou Yu Zhang Yucong Ma Shujin Du Lijie Fan Ruobing Niu Yingmei Zhang Ming He |
| author_sort | Can Cao |
| collection | DOAJ |
| description | Summary: Endometrial angiogenesis is necessary for good endometrial receptivity. Krüppel-like factor 4 (KLF4) is a transcription factor that is essential for regulating angiogenesis. Here we found that vascular endothelial growth factor A (VEGFA) can form a positive feedback loop with KLF4 to promote the proliferation and migration of human endometrial microvascular endothelial cells (HEMECs) and inhibit cell apoptosis. General control non-derepressible 5 (GCN5) is also time-dependent on VEGFA and participates in the KLF4-VEGFA loop. In addition, we found that GCN5 is a succinyltransferase that modulates the succinylation of histones and nonhistones. GCN5 interacts with KLF4 and is recruited to the KLF4-binding site of the VEGFA promoter to succinylate H3K79, which initiates gene transcription epigenetically. For nonhistones, GCN5 succinylates KLF4 that is activated by ERK signaling in HEMECs treated with VEGFA to increase its transcription activity. These results demonstrate KLF4-VEGFA positive feedback loop is regulated by epigenetics, which contributes to endometrial angiogenesis. |
| first_indexed | 2024-12-12T10:40:23Z |
| format | Article |
| id | doaj.art-32a6d8fc76344c1dba7d48cb40852242 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T10:40:23Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-32a6d8fc76344c1dba7d48cb408522422022-12-22T00:27:05ZengElsevieriScience2589-00422022-07-01257104509GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesisCan Cao0Yuling Zhou1Yu Zhang2Yucong Ma3Shujin Du4Lijie Fan5Ruobing Niu6Yingmei Zhang7Ming He8Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, ChinaHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, 3 Xing Yuan Road, Luquan, Shijiazhuang 050200, China; Corresponding authorSummary: Endometrial angiogenesis is necessary for good endometrial receptivity. Krüppel-like factor 4 (KLF4) is a transcription factor that is essential for regulating angiogenesis. Here we found that vascular endothelial growth factor A (VEGFA) can form a positive feedback loop with KLF4 to promote the proliferation and migration of human endometrial microvascular endothelial cells (HEMECs) and inhibit cell apoptosis. General control non-derepressible 5 (GCN5) is also time-dependent on VEGFA and participates in the KLF4-VEGFA loop. In addition, we found that GCN5 is a succinyltransferase that modulates the succinylation of histones and nonhistones. GCN5 interacts with KLF4 and is recruited to the KLF4-binding site of the VEGFA promoter to succinylate H3K79, which initiates gene transcription epigenetically. For nonhistones, GCN5 succinylates KLF4 that is activated by ERK signaling in HEMECs treated with VEGFA to increase its transcription activity. These results demonstrate KLF4-VEGFA positive feedback loop is regulated by epigenetics, which contributes to endometrial angiogenesis.http://www.sciencedirect.com/science/article/pii/S2589004222007805Biological sciencesMolecular biologyCell biology |
| spellingShingle | Can Cao Yuling Zhou Yu Zhang Yucong Ma Shujin Du Lijie Fan Ruobing Niu Yingmei Zhang Ming He GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis iScience Biological sciences Molecular biology Cell biology |
| title | GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis |
| title_full | GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis |
| title_fullStr | GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis |
| title_full_unstemmed | GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis |
| title_short | GCN5 participates in KLF4-VEGFA feedback to promote endometrial angiogenesis |
| title_sort | gcn5 participates in klf4 vegfa feedback to promote endometrial angiogenesis |
| topic | Biological sciences Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222007805 |
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