Characterization of the enzyme for 5-hydroxymethyluridine production and its role in silencing transposable elements in dinoflagellates

• 成果类型: Article
• 署名作者: Li, Chongping; Li, Ying; Wang, Yuci; Meng, Xiangrui; Shi, Xiaoyan; Zhang, Yangyi; Liang, Nan; Huang, Hongda; Li, Yue; Zhou, Hui; Xu, Jiawei; Xu, Wenqi; Chen, Hao
• 署名单位: Zhengzhou University; Henan Academy of Innovations in Medical Science; Southern University of Science & Technology; Southern University of Science & Technology; Fudan University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10633
• DOI: 10.1073/pnas.2400906121
• 发表日期: 2024-11-12
• 关键词: modified bases; dna; hydroxymethyluracil; biosynthesis; cytosine; thymine; uracil

摘要

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 Amphidinium carterae, 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.