A genome-wide screen reveals new regulators of the 2-cell-like cell state - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Nature Structural and Molecular Biology Année : 2023

A genome-wide screen reveals new regulators of the 2-cell-like cell state

Nikhil Gupta
Connectez-vous pour contacter l'auteur
Lounis Yakhou
Julien Richard Albert
Fumihito Miura
Takashi Ito
Maxim Greenberg

Résumé

In mammals, only the zygote and blastomeres of the early embryo are totipotent. This totipotency is mirrored in vitro by mouse ‘2-cell-like cells’ (2CLCs), which appear at low frequency in cultures of embryonic stem cells (ESCs). Because totipotency is not completely understood, we carried out a genome-wide CRISPR knockout screen in mouse ESCs, searching for mutants that reactivate the expression of Dazl, a gene expressed in 2CLCs. Here we report the identification of four mutants that reactivate Dazl and a broader 2-cell-like signature: the E3 ubiquitin ligase adaptor SPOP, the Zinc-Finger transcription factor ZBTB14, MCM3AP, a component of the RNA processing complex TREX-2, and the lysine demethylase KDM5C. All four factors function upstream of DPPA2 and DUX, but not via p53. In addition, SPOP binds DPPA2, and KDM5C interacts with ncPRC1.6 and inhibits 2CLC gene expression in a catalytic-independent manner. These results extend our knowledge of totipotency, a key phase of organismal life.

Domaines

Chimie

Dates et versions

pasteur-04181758 , version 1 (16-08-2023)

Identifiants

Citer

Nikhil Gupta, Lounis Yakhou, Julien Richard Albert, Anaelle Azogui, Laure Ferry, et al.. A genome-wide screen reveals new regulators of the 2-cell-like cell state. Nature Structural and Molecular Biology, 2023, 30 (8), pp.1105-1118. ⟨10.1038/s41594-023-01038-z⟩. ⟨pasteur-04181758⟩
71 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More