YTHDF2 Suppresses the 2C-like State in Mouse Embryonic Stem Cells via the DUX-ZSCAN4 Molecular Circuit

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108479 - 108479

Published: April 1, 2025

Mouse embryonic stem cells (ESCs) consist of a rare population heterogeneous 2-cell-like (2CLCs). These transiently recapitulate the transcriptional and epigenetic features 2-cell embryos, serving as unique model for studying totipotency acquisition development. Accumulating evidence has demonstrated that transcription factors modifications exert crucial functions in transition ESCs to 2CLCs. However, roles RNA modification regulation 2C-like state remain elusive. Using DUX-induced 2CLCs system, we examine N6-methyladenosine (m6A) landscape transcriptome-wide, observe dynamic m6A during DUX-driven reprogramming. Notably, many core 2C transcripts like Dux Zscan4, are highly methylated. We identify reader protein YTHDF2 critical regulator state. Depletion facilitates robust expressions 2C-signature genes ESCs-to-2CLCs transition. Intriguingly, binds subset m6A-modified promotes their decay. further demonstrate suppresses program manner is dependent on both DUX-ZSCAN4 molecular circuit. Mechanistically, interacts with CNOT1, key component deadenylase complex. Consistently, silencing CNOT1 upregulates Collectively, our findings reveal novel insights into epitranscriptomic mouse ESCs.

Language: Английский

RNA m⁶A modification regulates cell fate transition between pluripotent stem cells and 2‐cell‐like cells

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(9)

Published: July 1, 2024

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Language: Английский