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Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression

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机构： [1]The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041 Guangdong, China. [2]Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, 515041Guangdong, China. [3]Department of Parasitology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. [4]Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, 515051 Guangdong, China. [5]The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of ImmuneMicroenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. [6]Institute of Oncologic Pathology, Shantou University Medical College, Shantou, 515041 Guangdong, China. [7]The Laboratory for Cancer Molecular Biology, Shantou Academy of Medical Sciences, Shantou, 515041 Guangdong, China. [8]Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou, 515041 Guangdong, China.

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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.© 2025. The Author(s).

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第一作者：

第一作者机构： [1]The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041 Guangdong, China. [2]Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, 515041Guangdong, China.

通讯作者：

通讯机构： [1]The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041 Guangdong, China. [2]Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, 515041Guangdong, China. [6]Institute of Oncologic Pathology, Shantou University Medical College, Shantou, 515041 Guangdong, China. [7]The Laboratory for Cancer Molecular Biology, Shantou Academy of Medical Sciences, Shantou, 515041 Guangdong, China. [8]Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou, 515041 Guangdong, China.

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