53BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathway
Summary: p53-binding protein 1 (53BP1) participates in DNA damage repair through H4K20 di-methylation (H4K20me2)-mediated accumulation at DNA damage sites. However, it remains unclear whether H4K20me2-mediated 53BP1 chromatin binding regulates gene transcription in unstressed cells. Here, we demonst...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725009234 |
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| author | Yundong Fu Wei Wu Maosha Zhang Zeming Rong Bao Lin Xin Zhou Dingwei Li Xin Shi Jing Guo Shuyun Ma Qiang Chen |
| author_facet | Yundong Fu Wei Wu Maosha Zhang Zeming Rong Bao Lin Xin Zhou Dingwei Li Xin Shi Jing Guo Shuyun Ma Qiang Chen |
| author_sort | Yundong Fu |
| collection | DOAJ |
| description | Summary: p53-binding protein 1 (53BP1) participates in DNA damage repair through H4K20 di-methylation (H4K20me2)-mediated accumulation at DNA damage sites. However, it remains unclear whether H4K20me2-mediated 53BP1 chromatin binding regulates gene transcription in unstressed cells. Here, we demonstrate that 53BP1 depletion leads to a p53-dependent upregulation of E2F7. The direct interaction between 53BP1 and p53 is dispensable for this process, which is distinct from the established function of 53BP1-USP28-p53 complex. Notably, 53BP1 binds to E2F7 transcription start sites (TSSs) in an H4K20me2-dependent manner, which modulates p53’s binding ability through regulating epigenetic modifications at E2F7 TSS. Furthermore, our findings indicate that 53BP1 depletion represses the expression of E2F7 target genes, particularly genes involved in Fanconi anemia pathway (FA pathway), leading to cellular hypersensitivity to interstrand DNA crosslinks (ICLs). In summary, we identify 53BP1 as a negative regulator of p53-E2F7 axis, influencing the FA pathway through H4K20me2-mediated binding at E2F7 TSS. |
| format | Article |
| id | doaj-art-5d2aee5a99734fbfbe6ecdc513522a13 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-5d2aee5a99734fbfbe6ecdc513522a132025-08-20T03:38:24ZengElsevierCell Reports2211-12472025-08-0144811615210.1016/j.celrep.2025.11615253BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathwayYundong Fu0Wei Wu1Maosha Zhang2Zeming Rong3Bao Lin4Xin Zhou5Dingwei Li6Xin Shi7Jing Guo8Shuyun Ma9Qiang Chen10Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. ChinaDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. China; Corresponding authorDepartment of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, P.R. China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, P.R. China; Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, China; Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China; Corresponding authorSummary: p53-binding protein 1 (53BP1) participates in DNA damage repair through H4K20 di-methylation (H4K20me2)-mediated accumulation at DNA damage sites. However, it remains unclear whether H4K20me2-mediated 53BP1 chromatin binding regulates gene transcription in unstressed cells. Here, we demonstrate that 53BP1 depletion leads to a p53-dependent upregulation of E2F7. The direct interaction between 53BP1 and p53 is dispensable for this process, which is distinct from the established function of 53BP1-USP28-p53 complex. Notably, 53BP1 binds to E2F7 transcription start sites (TSSs) in an H4K20me2-dependent manner, which modulates p53’s binding ability through regulating epigenetic modifications at E2F7 TSS. Furthermore, our findings indicate that 53BP1 depletion represses the expression of E2F7 target genes, particularly genes involved in Fanconi anemia pathway (FA pathway), leading to cellular hypersensitivity to interstrand DNA crosslinks (ICLs). In summary, we identify 53BP1 as a negative regulator of p53-E2F7 axis, influencing the FA pathway through H4K20me2-mediated binding at E2F7 TSS.http://www.sciencedirect.com/science/article/pii/S2211124725009234CP: Molecular biology |
| spellingShingle | Yundong Fu Wei Wu Maosha Zhang Zeming Rong Bao Lin Xin Zhou Dingwei Li Xin Shi Jing Guo Shuyun Ma Qiang Chen 53BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathway Cell Reports CP: Molecular biology |
| title | 53BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathway |
| title_full | 53BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathway |
| title_fullStr | 53BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathway |
| title_full_unstemmed | 53BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathway |
| title_short | 53BP1 regulates p53-E2F7-dependent transcriptional gene repression and participates in the Fanconi anemia pathway |
| title_sort | 53bp1 regulates p53 e2f7 dependent transcriptional gene repression and participates in the fanconi anemia pathway |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725009234 |
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