Analysis of genome architecture during SCNT reveals a role of cohesin in impeding minor ZGA

Published: 27-05-2020| Version 3 | DOI: 10.17632/vyfpfvb2th.3
mickish zhang,
Dan-Ya Wu,
Hui Zheng,
Yao Wang,
Qiao-Ran Sun,
Xin Liu,
Li-Yan Wang,
Wen-Jing Xiong,
Qiujun Wang,
James Rhodes,
Kai Xu,
lijia li,
zili LIN,
Guang Yu,
Weikun Xia,
Bo Huang,
zhenhai du,
Yao Yao,
Kim A. Nasmyth,
Rob Klose,
Yi-Liang Miao,
Wei Xie


Somatic cell nuclear transfer (SCNT) can reprogram a somatic nucleus to a totipotent state. However, the re-organization of three-dimensional chromatin structure in this process remains poorly understood. Using low-input Hi-C, we revealed that during SCNT, the transferred nucleus first enters a mitotic-like state (premature chromatin condensation). Unlike fertilized embryos, SCNT embryos show stronger TADs at the 1-cell stage. TADs become weaker at the 2-cell stage, followed by gradual consolidation. Compartments A/B are markedly weak in 1-cell SCNT embryos and become increasingly strengthened afterward. By the 8-cell stage, somatic chromatin architecture is largely reset to embryonic patterns. Unexpectedly, we found cohesin represses minor zygotic genome activation (ZGA) genes (2-cell specific genes) in pluripotent and differentiated cells, and pre-depleting cohesin in donor cells facilitates minor ZGA and SCNT. These data reveal multi-step reprogramming of 3D chromatin architecture during SCNT and support dual roles of cohesin in TAD formation and minor ZGA repression.