ENAGenomicsScience and Technology, Kwansei Gakuin Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA556017Mus musculusThe 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 remains elusive. Here, we identified C-terminal binding protein 1/2 (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 primed to naïve pluripotency transition. Furthermore, CtBP1/2 also interacted with the PRC2 complexes, and the loss of Ctbp1/2 impaired the PRC2 and H3K27me3 enrichment at the target genes upon PRDM14 overexpression. These results suggest that evidence that the target gene-dependent transcriptional activity of PRDM14 is regulated by partner switching to ensure transition from primed to naïve pluripotency. Overall design: We anlalyzed 8 samples on two strip of microarray detected by GeneAtlas.ENAfalseExpression data of PRDM14 overexpression in WT, Suz12 KO and Ctbp1/2 DKO ESCsExpression data of PRDM14 overexpression in WT, Suz12 KO and Ctbp1/2 DKO ESCs2025-09-242020-07-16PRJNA556017GSE13466610090