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

Published: 27 May 2020| Version 3 | DOI: 10.17632/vyfpfvb2th.3
Contributors:
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

Description

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.

Files

Institutions

Tsinghua University

Categories

Early Embryonic Development, Chromatin

License