CTCF is a barrier for 2C-like reprogramming.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 08 2021
11 08 2021
Historique:
received:
05
01
2021
accepted:
17
07
2021
entrez:
12
8
2021
pubmed:
13
8
2021
medline:
24
8
2021
Statut:
epublish
Résumé
Totipotent cells have the ability to generate embryonic and extra-embryonic tissues. Interestingly, a rare population of cells with totipotent-like potential, known as 2 cell (2C)-like cells, has been identified within ESC cultures. They arise from ESC and display similar features to those found in the 2C embryo. However, the molecular determinants of 2C-like conversion have not been completely elucidated. Here, we show that the CCCTC-binding factor (CTCF) is a barrier for 2C-like reprogramming. Indeed, forced conversion to a 2C-like state by the transcription factor DUX is associated with DNA damage at a subset of CTCF binding sites. Depletion of CTCF in ESC efficiently promotes spontaneous and asynchronous conversion to a 2C-like state and is reversible upon restoration of CTCF levels. This phenotypic reprogramming is specific to pluripotent cells as neural progenitor cells do not show 2C-like conversion upon CTCF-depletion. Furthermore, we show that transcriptional activation of the ZSCAN4 cluster is necessary for successful 2C-like reprogramming. In summary, we reveal an unexpected relationship between CTCF and 2C-like reprogramming.
Identifiants
pubmed: 34381034
doi: 10.1038/s41467-021-25072-x
pii: 10.1038/s41467-021-25072-x
pmc: PMC8358036
doi:
Substances chimiques
CCCTC-Binding Factor
0
Ctcf protein, mouse
0
Homeodomain Proteins
0
Transcription Factors
0
Zscan4c protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4856Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM142792
Pays : United States
Informations de copyright
© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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