Monitoring rapid degradation of NANOG reveals UTP15 maintains pluripotency by regulating nascent transcripts
Master transcription factors (MTFs) are key regulators in cell fate determination. However, an approach to profile MTF's direct transcriptional targets together with their associated RNA-binding proteins (RBPs), is still lacking. Here, we applied 5-ethynyluridine RNA metabolic labeling and click chemistry to map the dynamics of the transcriptional targets and the RBPs interacting with the newly transcribed RNAs upon acute NANOG degradation in mouse embryonic stem cells (mESCs). We identified UTP15, a classic rRNA-biogenesis regulator, acts as a key activator of pluripotency-associated gene transcription independently of rRNA biogenesis. Importantly, NANOG-regulated transcription enhances UTP15 binding to transcription start sites (TSSs), associated with increased Pol II binding and more active transcription. Moreover, UTP15 promotes the assembly of Pol II biomolecular condensates, thereby potentially driving pluripotency gene transcription. Collectively, our study uncovers a NANOG-nascent transcript-UTP15 regulatory axis to activate pluripotency gene transcription, providing a distinct approach for studying MTF's function during cell fate determination.
Authors
- Dajiang Qin
- Xiwei Wang (ORCID: https://orcid.org/0000-0002-3970-1336)
- Chuanman Zhou (ORCID: https://orcid.org/0000-0003-4770-6150)
- Yu Zhao (ORCID: https://orcid.org/0000-0002-0349-7206)
- Mingqiang Deng
- Qiuyue Zhu (ORCID: https://orcid.org/0000-0003-1394-2999)
- Jinxin Xu (ORCID: https://orcid.org/0000-0002-1680-7533)
- Lishen Wang
- Zhibiao Mai (ORCID: https://orcid.org/0000-0002-7931-7363)
- Bin Dong (ORCID: https://orcid.org/0000-0003-4051-7306)
- Yuting Yuan (ORCID: https://orcid.org/0000-0001-5431-1478)
- Yu-Ling Song (ORCID: https://orcid.org/0000-0002-7946-6051)
- Hui Zheng (ORCID: https://orcid.org/0000-0001-6801-0529)
- Cristin G. Print (ORCID: https://orcid.org/0000-0001-8345-7812)
- Qiongfang Wu (ORCID: https://orcid.org/0000-0002-8432-7240)
- Xichen Bao (ORCID: https://orcid.org/0000-0003-0389-4233)
- Ralf Jauch (ORCID: https://orcid.org/0000-0002-6590-9579)
- Jinkai Wang (ORCID: https://orcid.org/0000-0002-2577-7575)
- Guangming Wu (ORCID: https://orcid.org/0000-0003-1923-7609)
- Wensheng Zhang (ORCID: https://orcid.org/0000-0002-6876-3173)
- Yulong Zhang (ORCID: https://orcid.org/0000-0002-9857-8884)
- Luyao Pan
- Peng Tang (ORCID: https://orcid.org/0000-0003-3580-7667)
- Dongjun Liu
- Dongmei He (ORCID: https://orcid.org/0009-0002-4099-441X)
- Zhi Xiong
- Duo Li
- Yanlin Hou
- Zhengwen Nie
Institutions
- Shandong University of Technology (CN)
- Department of Health (CN)
- Shandong University of Aeronautics (CN)
- University of Auckland (NZ)
- Sun Yat-sen University (CN)
- Chinese University of Hong Kong (HK)
- Chinese Academy of Sciences (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Third Affiliated Hospital of Guangzhou Medical University (CN)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN)
- Guangzhou Automobile Group (China) (CN)
- Maurice Wilkins Centre (NZ)
- Sun Yat-sen University Cancer Center (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Shandong First Medical University (CN)
- University of Chinese Academy of Sciences (CN)
- University of Hong Kong (HK)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-08
- DOI
- https://doi.org/10.1038/s41467-025-67018-7
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00