Three-dimensional folding dynamics of the Xenopus tropicalis genome

• Published in: Nature genetics Vol. 53; no. 7; pp. 1075 - 1087
• Main Authors: Niu, Longjian, Shen, Wei, Shi, Zhaoying, Tan, Yongjun, He, Na, Wan, Jing, Sun, Jialei, Zhang, Yuedong, Huang, Yingzhang, Wang, Wenjing, Fang, Chao, Li, Jiashuo, Zheng, Piaopiao, Cheung, Edwin, Chen, Yonglong, Li, Li, Hou, Chunhui
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2021; Nature Publishing Group
• Subjects: 631/114; 631/136; 631/208; 631/337; 631/80; Agriculture; Animal Genetics and Genomics; Animals; Apoptosis Regulatory Proteins - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Cycle Proteins - genetics; Cell division; Chromatin - genetics; Chromatin - metabolism; Chromatin Assembly and Disassembly; Chromatin remodeling; Chromosomes; Computational Biology - methods; Conformation; Deoxyribonucleic acid; DNA; Embryonic development; Embryonic Development - genetics; Embryos; Gene expression; Gene Expression Regulation, Developmental; Gene Function; Gene Knockdown Techniques; Gene silencing; Genetic aspects; Genome; Genomes; Genomics - methods; Human Genetics; Models, Molecular; Nucleic Acid Conformation; Occupancy; Phenotype; Physiological aspects; Principal components analysis; Proteins; RNA polymerase; Structure; Transcription activation; Xenopus; Xenopus - embryology; Xenopus - genetics; Xenopus Proteins - genetics; Xenopus tropicalis; China
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/s41588-021-00878-z

Animal interphase chromosomes are organized into topologically associating domains (TADs). How TADs are formed is not fully understood. Here, we combined high-throughput chromosome conformation capture and gene silencing to obtain insights into TAD dynamics in Xenopus tropicalis embryos. First, TAD establishment in X. tropicalis is similar to that in mice and flies and does not depend on zygotic genome transcriptional activation. This process is followed by further refinements in active and repressive chromatin compartments and the appearance of loops and stripes. Second, within TADs, higher self-interaction frequencies at one end of the boundary are associated with higher DNA occupancy of the architectural proteins CTCF and Rad21. Third, the chromatin remodeling factor ISWI is required for de novo TAD formation. Finally, TAD structures are variable in different tissues. Our work shows that X. tropicalis is a powerful model for chromosome architecture analysis and suggests that chromatin remodeling plays an essential role in de novo TAD establishment. Hi-C and single-molecule sequencing analysis provide an improved assembly of the Xenopus tropicalis genome and insights into three-dimensional genome dynamics throughout embryogenesis.