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Updated: Aug 5, 2026
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Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
Published on: April 27, 2017
CtBP1/2 restrict DUX-dependent and independent 2C-like programs in mouse embryonic stem cells
Kazuma Yoshioka1, Maki Ichisakino1, Kota Sugiyama1
1Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Hyogo, Japan.
EMBO Reports
|August 3, 2026
Summary
C-terminal binding protein 1/2 (CtBP1/2) normally represses key early embryonic gene activation. Disrupting CtBP1/2 in mouse stem cells unlocks both DUX-dependent and DUX-independent developmental programs.
Area of Science:
- Developmental Biology
- Epigenetics
- Gene Regulation
Background:
- Zygotic genome activation (ZGA) is crucial for early embryonic development in mice, following maternal mRNA clearance.
- 2-cell-like cells (2CLCs) model early embryonic transcription but may not fully represent DUX-independent pathways.
Purpose of the Study:
- To investigate the role of C-terminal binding protein 1/2 (CtBP1/2) in regulating early embryonic transcriptional programs.
- To explore DUX-independent pathways in mouse embryonic stem cells.
Main Methods:
- Disruption of CtBP1/2 in mouse embryonic stem cells.
- Analysis of DUX-dependent and DUX-independent gene expression.
- Overexpression of Pramel7 (PRAMEL7) to assess rescue effects.
Main Results:
- CtBP1/2 disruption activates both DUX-dependent minor ZGA and DUX-independent major ZGA/post-ZGA programs.
- PRAMEL7 is derepressed independently of DUX and contributes to both transcriptional programs.
- PRAMEL7 overexpression partially rescues DUX deletion defects, linked to UHRF1 downregulation and DNA demethylation.
Conclusions:
- CtBP1/2 acts as a repressor of multiple early embryonic transcriptional programs.
- CtBP1/2 and PRAMEL7 play significant roles in DUX-independent developmental pathways.
