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Updated: Dec 15, 2025
Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Published on: June 28, 2018
The PRDM14-CtBP1/2-PRC2 complex regulates transcriptional repression during the transition from primed to naïve
Maiko Yamamoto1, Yoshiaki Suwa1, Kohta Sugiyama1
1Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Insights
PRDM14 maintains pluripotency through transcriptional regulation. New findings reveal C-terminal binding proteins (CtBP1/2) mediate PRDM14 repression, crucial for pluripotency maintenance and cell state transitions.
Area of Science:
- Developmental Biology
- Epigenetics
- Molecular Biology
Background:
- Pluripotency is maintained by transcriptional networks, with PRDM14 regulating gene expression.
- The precise mechanisms of PRDM14's dual role in gene activation and repression are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms behind PRDM14's target gene-dependent transcriptional control.
- To identify factors involved in PRDM14-mediated gene repression.
Main Methods:
- Co-immunoprecipitation assays to identify protein interactions.
- Gene expression analysis and chromatin immunoprecipitation (ChIP) to assess transcriptional regulation and epigenetic modifications.
- CRISPR/Cas9 gene editing to study the function of CtBP1/2 in cell models.
Main Results:
- C-terminal binding protein 1 and 2 (CtBP1/2) were identified as key components of the PRDM14 repressive complex, dependent on CBFA2T2.
- Loss of CtBP1/2 disrupted PRDM14-mediated repression essential for pluripotency maintenance and the transition from primed to naïve pluripotency.
- CtBP1/2 interaction with Polycomb repressive complex 2 (PRC2) was demonstrated, and its absence impaired PRC2 enrichment and H3K27me3 modification at target genes.
Conclusions:
- PRDM14's context-dependent transcriptional activity is regulated by partner switching, involving CtBP1/2 and PRC2.
- This regulatory mechanism is critical for maintaining pluripotency and facilitating cell state transitions.
- The findings reveal a novel layer of epigenetic control governing pluripotency.
Abstract:
The pluripotency-associated transcriptional network is regulated by a core circuitry of transcription factors. The PR domain-containing protein PRDM14 maintains pluripotency by activating and repressing transcription in a target gene-dependent manner. However, the mechanisms underlying dichotomic switching of PRDM14-mediated transcriptional control remain elusive. Here, we identified C-terminal binding protein 1 and 2 (CtBP1 and CtBP2; generically referred to as CtBP1/2) as components of the PRDM14-mediated repressive complex. CtBP1/2 binding to PRDM14 depends on CBFA2T2, a core component of the PRDM14 complex. The loss of Ctbp1/2 impaired the PRDM14-mediated transcriptional repression required for pluripotency maintenance and transition from primed to naïve pluripotency. Furthermore, CtBP1/2 interacted with the PRC2 complexes, and the loss of Ctbp1/2 impaired Polycomb repressive complex 2 (PRC2) and H3K27me3 enrichment at target genes after Prdm14 induction. These results provide evidence that the target gene-dependent transcriptional activity of PRDM14 is regulated by partner switching to ensure the transition from primed to naïve pluripotency.This article has an associated First Person interview with the first author of the paper.
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