Impact Factor:17.97

DOI number:10.1016/j.molcel.2020.06.001

Journal:Molecular Cell (B刊)

Abstract:Somatic cell nuclear transfer (SCNT) can reprogram a somatic nucleus to a totipotent state. However, the re-organization of 3D 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 topologically associating domains (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.

Co-author:Sun QR,Liu X,Wang LY,Xiong WJ,Wang QJ,Rhodes JDP,Xu K,Li LJ,Lin ZL,Yu G,Xia WK,Huang B,Du ZH,Yao Y,Nasmyth KA,Klose RJ

First Author:Wang Y#,Zheng H#,Wu DY#,Zhang K#

Indexed by:Journal paper

Correspondence Author:Miao YL*,Xie W*

Volume:79

Issue:2

Page Number:234-250.e9.

Translation or Not:no

Date of Publication:2020-07-16

Included Journals:SCI

Links to published journals:https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30386-5