Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplex
Abstract Accumulating evidence indicates that G‐quadruplexes (G4s) are involved in transcriptional regulation. Previous studies have demonstrated that DHX36 preferentially resolves G4s, suggesting its potential impact on gene transcription mediated by these structures. However, systematic validation...
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Wiley
2025-01-01
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| Online Access: | https://doi.org/10.1002/agt2.647 |
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| author | Ziang Lu Jinglei Xu Yuqi Chen Yuanyuan Zhou Xiaolu Zhou Qi Wang Qi Wei Shaoqing Han Ruiqi Zhao Xiaocheng Weng Xiaolian Zhang Xiang Zhou |
| author_facet | Ziang Lu Jinglei Xu Yuqi Chen Yuanyuan Zhou Xiaolu Zhou Qi Wang Qi Wei Shaoqing Han Ruiqi Zhao Xiaocheng Weng Xiaolian Zhang Xiang Zhou |
| author_sort | Ziang Lu |
| collection | DOAJ |
| description | Abstract Accumulating evidence indicates that G‐quadruplexes (G4s) are involved in transcriptional regulation. Previous studies have demonstrated that DHX36 preferentially resolves G4s, suggesting its potential impact on gene transcription mediated by these structures. However, systematic validation is required to establish a link between DHX36 activity and its roles in transcriptional regulation. In this study, we investigate the role of DHX36 in transcription. First, we employ the cleavage under targets and tagmentation (CUT&Tag), an efficient method for mapping protein–DNA interactions, to identify the binding sites in the chromatin of MCF‐7 cells. Subsequently, we use the auxin‐inducible degron (AID) protein degradation system and improved nascent RNA sequencing method acrylonitrile‐mediated uridine‐to‐cytidine conversion sequencing (AMUC‐seq) to pinpoint genes directly regulated by DHX36. Our results reveal a significant enrichment of G4 structures at DHX36 target sites, predominantly located in active genomic regions. In vitro assays further demonstrate DHX36's interaction with G4 sequences from three specific oncogenes. These findings underscore the potential role of DHX36 in modulating gene transcription through G4 structures. |
| format | Article |
| id | doaj-art-64f89c33f7c84742a79b82f1da1e62fb |
| institution | Kabale University |
| issn | 2692-4560 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
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| spelling | doaj-art-64f89c33f7c84742a79b82f1da1e62fb2025-01-21T08:57:07ZengWileyAggregate2692-45602025-01-0161n/an/a10.1002/agt2.647Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplexZiang Lu0Jinglei Xu1Yuqi Chen2Yuanyuan Zhou3Xiaolu Zhou4Qi Wang5Qi Wei6Shaoqing Han7Ruiqi Zhao8Xiaocheng Weng9Xiaolian Zhang10Xiang Zhou11College of Chemistry and Molecular SciencesDepartment of Hematology of Zhongnan HospitalTaikang Center for Life and Medical SciencesWuhan UniversityWuhanHubeiPeople's Republic of ChinaCollege of Chemistry and Molecular SciencesDepartment of Hematology of Zhongnan HospitalTaikang Center for Life and Medical SciencesWuhan UniversityWuhanHubeiPeople's Republic of ChinaCollege of Chemistry and Molecular SciencesDepartment of Hematology of Zhongnan HospitalTaikang Center for Life and Medical SciencesWuhan UniversityWuhanHubeiPeople's Republic of ChinaState Key Laboratory of Virology and Medical Research InstituteHubei Province Key Laboratory of Allergy and Immunology and Department of ImmunologyWuhan University School of MedicineWuhanHubeiPeople's Republic of ChinaCollege of Chemistry and Molecular SciencesDepartment of Hematology of Zhongnan HospitalTaikang Center for Life and Medical SciencesWuhan UniversityWuhanHubeiPeople's Republic of ChinaDepartment of HematologyZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanHubeiPeople's Republic of ChinaCollege of Chemistry and Molecular SciencesDepartment of Hematology of Zhongnan HospitalTaikang Center for Life and Medical SciencesWuhan UniversityWuhanHubeiPeople's Republic of ChinaCollege of Chemistry and Molecular SciencesDepartment of Hematology of Zhongnan HospitalTaikang Center for Life and Medical SciencesWuhan UniversityWuhanHubeiPeople's Republic of ChinaKey Laboratory of Biomedical Polymers‐Ministry of EducationCollege of Chemistry and Molecular Sciences Wuhan University Wuhan Hubei People's Republic of ChinaKey Laboratory of Biomedical Polymers‐Ministry of EducationCollege of Chemistry and Molecular Sciences Wuhan University Wuhan Hubei People's Republic of ChinaState Key Laboratory of Virology and Medical Research InstituteHubei Province Key Laboratory of Allergy and Immunology and Department of ImmunologyWuhan University School of MedicineWuhanHubeiPeople's Republic of ChinaCollege of Chemistry and Molecular SciencesDepartment of Hematology of Zhongnan HospitalTaikang Center for Life and Medical SciencesWuhan UniversityWuhanHubeiPeople's Republic of ChinaAbstract Accumulating evidence indicates that G‐quadruplexes (G4s) are involved in transcriptional regulation. Previous studies have demonstrated that DHX36 preferentially resolves G4s, suggesting its potential impact on gene transcription mediated by these structures. However, systematic validation is required to establish a link between DHX36 activity and its roles in transcriptional regulation. In this study, we investigate the role of DHX36 in transcription. First, we employ the cleavage under targets and tagmentation (CUT&Tag), an efficient method for mapping protein–DNA interactions, to identify the binding sites in the chromatin of MCF‐7 cells. Subsequently, we use the auxin‐inducible degron (AID) protein degradation system and improved nascent RNA sequencing method acrylonitrile‐mediated uridine‐to‐cytidine conversion sequencing (AMUC‐seq) to pinpoint genes directly regulated by DHX36. Our results reveal a significant enrichment of G4 structures at DHX36 target sites, predominantly located in active genomic regions. In vitro assays further demonstrate DHX36's interaction with G4 sequences from three specific oncogenes. These findings underscore the potential role of DHX36 in modulating gene transcription through G4 structures.https://doi.org/10.1002/agt2.647G‐quadruplexnascent RNAprotein degradationtranscription |
| spellingShingle | Ziang Lu Jinglei Xu Yuqi Chen Yuanyuan Zhou Xiaolu Zhou Qi Wang Qi Wei Shaoqing Han Ruiqi Zhao Xiaocheng Weng Xiaolian Zhang Xiang Zhou Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplex Aggregate G‐quadruplex nascent RNA protein degradation transcription |
| title | Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplex |
| title_full | Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplex |
| title_fullStr | Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplex |
| title_full_unstemmed | Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplex |
| title_short | Rapid degradation of DHX36 revealing its transcriptional role by interacting with G‐quadruplex |
| title_sort | rapid degradation of dhx36 revealing its transcriptional role by interacting with g quadruplex |
| topic | G‐quadruplex nascent RNA protein degradation transcription |
| url | https://doi.org/10.1002/agt2.647 |
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