Journal
JOURNAL OF CELL SCIENCE
Volume 133, Issue 15, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.240176
Keywords
PRDM14-CtBP1/2-PRC2 complex; Transcriptional repression; Pluripotency; Embryonic stem cells
Categories
Funding
- Japan Society for the Promotion of Science KAKENHI [24681040, 18H02422]
- Promotion of Joint International Research (Japan Society for the Promotion of Science KAKENHI) [15KK0262]
- Scientific Research on Innovative Areas, 'Epigenome dynamics and regulation in germ cells' (Ministry of Education, Culture, Sports, Science, and Technology KAKENHI) [26112514, 16H01223]
- Scientific Research on Innovative Areas, 'Mechanisms regulating gamete formation in animals' (Ministry of Education, Culture, Sports, Science, and Technology KAKENHI) [16H01258]
- Scientific Research on Innovative Areas, 'Program of totipotency: From decoding to designing' (Ministry of Education, Culture, Sports, Science, and Technology KAKENHI) [20H05375]
- program of the Joint Usage/Research Center for Developmental Medicine, Institute of Molecular Embryology and Genetics of Kumamoto University
- Grants-in-Aid for Scientific Research [20H05375, 24681040, 16H01258, 15KK0262, 16H01223, 26112514, 18H02422] Funding Source: KAKEN
Ask authors/readers for more resources
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 naive 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 naive pluripotency. This article has an associated First Person interview with the first author of the paper
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available