Analysis of Genome Architecture during SCNT Reveals a Role of Cohesin in Impeding Minor ZGA.
Animals
Cell Cycle Proteins
/ physiology
Cell Line
Cell Nucleus
Chromatin
/ physiology
Chromatin Assembly and Disassembly
Chromosomal Proteins, Non-Histone
/ physiology
Computational Biology
/ methods
Datasets as Topic
Embryonic Development
Female
Male
Mice
Mice, Inbred C57BL
Nuclear Transfer Techniques
Zygote
/ physiology
Cohesins
Hi-C
SCNT
TAD
chromatin reprogramming
cohesin
early embryo
minor ZGA
somatic cell nuclear transfer
three-dimensional chromatin structure
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
16 07 2020
16 07 2020
Historique:
received:
25
10
2019
revised:
27
05
2020
accepted:
28
05
2020
pubmed:
25
6
2020
medline:
1
9
2020
entrez:
25
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32579944
pii: S1097-2765(20)30386-5
doi: 10.1016/j.molcel.2020.06.001
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
234-250.e9Subventions
Organisme : Wellcome Trust
ID : 209400/Z/17/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.