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Systematic Chromatin Architecture Analysis in Xenopus tropicalis Reveals Conserved Three-Dimensional Folding Principles of Vertebrate Genomes

By Longjian Niu, Wei Shen, Zhaoying Shi, Na He, Jing Wan, Jialei Sun, Yuedong Zhang, Yingzhang Huang, Wenjing Wang, Chao Fang, Jiashuo Li, Piaopiao Zheng, Edwin Cheung, Yonglong Chen, Li Li, Chunhui Hou

Posted 02 Apr 2020
bioRxiv DOI: 10.1101/2020.04.02.021378

Metazoan genomes are folded into 3D structures in interphase nuclei. However, the molecular mechanism remains unknown. Here, we show that topologically associating domains (TADs) form in two waves during Xenopus tropicalis embryogenesis, first at zygotic genome activation and then as the expression of CTCF and Rad21 is elevated. We also found TAD structures continually change for at least three times during development. Surprisingly, the directionality index is preferentially stronger on one side of TADs where orientation-biased CTCF and Rad21 binding are observed, a conserved pattern that is found in human cells as well. Depletion analysis revealed CTCF, Rad21, and RPB1, a component of RNAPII, are required for the establishment of TADs. Overall, our work shows that Xenopus is a powerful model for chromosome architecture analysis. Furthermore, our findings indicate that cohesin-mediated extrusion may anchor at orientation-biased CTCF binding sites, supporting a CTCF-anchored extrusion model as the mechanism for TAD establishment.

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