Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression
Abstract Anillin (ANLN), a mitotic protein that regulates contractile ring assembly, has been reported as an oncoprotein. However, the function of ANLN in cancer cells, especially in the nucleus, has not been fully understood. Here, we report a role of nuclear ANLN in gene transcriptional regulation...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56645-9 |
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| author | Yu-Fei Cao Hui Wang Yong Sun Bei-Bei Tong Wen-Qi Shi Liu Peng Yi-Meng Zhang Yu-Qiu Wu Teng Fu Hua-Yan Zou Kai Zhang Li-Yan Xu En-Min Li |
| author_facet | Yu-Fei Cao Hui Wang Yong Sun Bei-Bei Tong Wen-Qi Shi Liu Peng Yi-Meng Zhang Yu-Qiu Wu Teng Fu Hua-Yan Zou Kai Zhang Li-Yan Xu En-Min Li |
| author_sort | Yu-Fei Cao |
| collection | DOAJ |
| description | Abstract Anillin (ANLN), a mitotic protein that regulates contractile ring assembly, has been reported as an oncoprotein. However, the function of ANLN in cancer cells, especially in the nucleus, has not been fully understood. Here, we report a role of nuclear ANLN in gene transcriptional regulation. We find that nuclear ANLN directly interacts with the RNA polymerase II (Pol II) large subunit to form transcriptional condensates. ANLN enhances initiated Pol II clustering and promotes Pol II CTD phase separation. Short-term depletion of ANLN alters the chromatin binding and enhancer-mediated transcriptional activity of Pol II. The target genes of ANLN-Pol II axis are involved in oxidoreductase activity, Wnt signaling and cell differentiation. THZ1, a super-enhancer inhibitor, specifically inhibits ANLN-Pol II clustering, target gene expression and esophageal squamous cell carcinoma (ESCC) cell proliferation. Our results reveal the function of nuclear ANLN in transcriptional regulation, providing a theoretical basis for ESCC treatment. |
| format | Article |
| id | doaj-art-64ce04f1c52e4a23b127ab91d68e48fe |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-64ce04f1c52e4a23b127ab91d68e48fe2025-02-02T12:33:14ZengNature PortfolioNature Communications2041-17232025-02-0116111910.1038/s41467-025-56645-9Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expressionYu-Fei Cao0Hui Wang1Yong Sun2Bei-Bei Tong3Wen-Qi Shi4Liu Peng5Yi-Meng Zhang6Yu-Qiu Wu7Teng Fu8Hua-Yan Zou9Kai Zhang10Li-Yan Xu11En-Min Li12The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouDepartment of Parasitology, College of Veterinary Medicine, Sichuan Agricultural UniversityThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouDepartment of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, ShantouThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouThe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityChaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, ShantouThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, ShantouAbstract Anillin (ANLN), a mitotic protein that regulates contractile ring assembly, has been reported as an oncoprotein. However, the function of ANLN in cancer cells, especially in the nucleus, has not been fully understood. Here, we report a role of nuclear ANLN in gene transcriptional regulation. We find that nuclear ANLN directly interacts with the RNA polymerase II (Pol II) large subunit to form transcriptional condensates. ANLN enhances initiated Pol II clustering and promotes Pol II CTD phase separation. Short-term depletion of ANLN alters the chromatin binding and enhancer-mediated transcriptional activity of Pol II. The target genes of ANLN-Pol II axis are involved in oxidoreductase activity, Wnt signaling and cell differentiation. THZ1, a super-enhancer inhibitor, specifically inhibits ANLN-Pol II clustering, target gene expression and esophageal squamous cell carcinoma (ESCC) cell proliferation. Our results reveal the function of nuclear ANLN in transcriptional regulation, providing a theoretical basis for ESCC treatment.https://doi.org/10.1038/s41467-025-56645-9 |
| spellingShingle | Yu-Fei Cao Hui Wang Yong Sun Bei-Bei Tong Wen-Qi Shi Liu Peng Yi-Meng Zhang Yu-Qiu Wu Teng Fu Hua-Yan Zou Kai Zhang Li-Yan Xu En-Min Li Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression Nature Communications |
| title | Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression |
| title_full | Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression |
| title_fullStr | Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression |
| title_full_unstemmed | Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression |
| title_short | Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression |
| title_sort | nuclear anln regulates transcription initiation related pol ii clustering and target gene expression |
| url | https://doi.org/10.1038/s41467-025-56645-9 |
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