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 1/2 (CtBP1/2) as a component 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 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.
PRDM14-CtBP1/2-PRC2 complex regulates transcriptional repression during transition from primed to naïve pluripotency
Co-first authors
Present address: Laboratory of Epigenome Dynamics, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan
Currently Viewing Accepted Manuscript - Newer Version Available
Maiko Yamamoto, Yoshiaki Suwa, Kohta Sugiyama, Naoki Okashita, Masanori Kawaguchi, Naoki Tani, Kazumi Matsubara, Akira Nakamura, Yoshiyuki Seki; PRDM14-CtBP1/2-PRC2 complex regulates transcriptional repression during transition from primed to naïve pluripotency. J Cell Sci 2020; jcs.240176. doi: https://doi.org/10.1242/jcs.240176
Download citation file:
Advertisement
Introducing our new Editors
We welcome three new Editors to Journal of Cell Science - Robert Parton, Richa Rikhy and Simon Cook. You can read more about them in the Editorial from our Editor-in-Chief Michael Way.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Final registration deadline: 3 May 2024.
Workshop: Physics of the Early Embryonic Cell Divisions
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 11-14 November 2024. Application deadline: 17 May.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.
Propose a new Workshop for 2026
We are now accepting proposals for our 2026 Workshops programme. We aim to be responsive to the community and open to novel initiatives, so if you have a new idea for a biological workshop that you feel would work well, please apply. Applications deadline: 19 July 2024.