Characterization of the enzyme for 5-hydroxymethyluridine production and its role in silencing transposable elements in dinoflagellates
Dinoflagellate chromosomes are extraordinary, as their organization is independent of architectural nucleosomes unlike typical eukaryotes and shows a cholesteric liquid crystal state. 5-hydroxymethyluridine (5hmU) is present at unusually high levels and its function remains an enigma in dinoflagellates chromosomal DNA for several decades. Here, we demonstrate that 5hmU contents vary among different dinoflagellates and are generated through thymidine hydroxylation. Importantly, we identified the enzyme, which is a putative dinoflagellate TET/JBP homolog, catalyzing 5hmU production using both in vivo and in vitro biochemical assays. Based on the near-chromosomal level genome assembly of dinoflagellate <i>Amphidinium carterae</i>, we depicted a comprehensive 5hmU landscape and found that 5hmU loci are significantly enriched in repeat elements. Moreover, inhibition of 5hmU via dioxygenase inhibitor leads to transcriptional activation of 5hmU-marked transposable elements, implying that 5hmU appears to serve as an epigenetic mark for silencing transposon. Together, our results revealed the biogenesis, genome-wide landscape, and molecular function of dinoflagellate 5hmU, providing mechanistic insight into the function of this enigmatic DNA mark.
Authors
- Hui Zhou (ORCID: https://orcid.org/0000-0002-1509-0673)
- Xiangrui Meng (ORCID: https://orcid.org/0000-0001-5058-8701)
- Yuci Wang
- Nan Liang (ORCID: https://orcid.org/0000-0001-5828-8156)
- Hao Chen (ORCID: https://orcid.org/0000-0002-2534-9650)
- Jiawei Xu
- Yangyi Zhang (ORCID: https://orcid.org/0009-0001-2606-7401)
- Hongda Huang (ORCID: https://orcid.org/0000-0002-5376-4747)
- Chongping Li (ORCID: https://orcid.org/0000-0001-9958-6467)
- Ying Li
- Xiaoyan Shi (ORCID: https://orcid.org/0009-0008-8755-8280)
- Wenqi Xu (ORCID: https://orcid.org/0000-0003-2825-7740)
Institutions
- Sun Yat-sen University (CN)
- Fudan University (CN)
- National Health and Family Planning Commission (CN)
- Southern University of Science and Technology (CN)
- Guangdong University of Education (CN)
- Zhongshan Hospital (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-11-07
- DOI
- https://doi.org/10.1073/pnas.2400906121
- Citations
- 4
- Primary Topic
- Protist diversity and phylogeny
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- National Natural Science Foundation of China
- Sun Yat-sen University
- Fudan University
- Health and Family Planning Commission of Guangdong Province
- Zhengzhou University
- Southern University of Science and Technology
- First Affiliated Hospital of Zhengzhou University
- National Health Commission of the People's Republic of China
- National Key Research and Development Program of China