Nanog mediates erasure of imprint-associated epigenetic marks via Prdm14
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE214862 | GEO | 2023/10/01
REPOSITORIES: GEO
Similar Datasets
Project description:Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell (ESC) pluripotency and primordial germ cell (PGC) formation. It exerts its function, at least in part, through repressing genes associated with epigenetic modification and cell differentiation. Here, we show that this repressive function is mediated through an ETO-family co-repressor Mtgr1, which tightly binds to the pre-SET/SET domains of Prdm14 and co-occupies its genomic targets in mouse ESCs. Structure-guided point mutants abrogated the Prdm14-Mtgr1 association and disrupted Prdm14's function in mESC gene expression and PGC formation in vitro. Altogether, our work uncovers the molecular mechanism underlying Prdm14-mediated repression.
2016-01-01 | GSE74547 | GEO
Project description:Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell (ESC) pluripotency and primordial germ cell (PGC) formation. It exerts its function, at least in part, through repressing genes associated with epigenetic modification and cell differentiation. Here, we show that this repressive function is mediated through an ETO-family co-repressor Mtgr1, which tightly binds to the pre-SET/SET domains of Prdm14 and co-occupies its genomic targets in mouse ESCs. Structure-guided point mutants abrogated the Prdm14-Mtgr1 association and disrupted Prdm14's function in mESC gene expression and PGC formation in vitro. Altogether, our work uncovers the molecular mechanism underlying Prdm14-mediated repression. Examination of Prdm14 and Mtgr1 occupancy by ChIP-seq and effects on gene expression in mouse embryonic stem cells
2016-07-03 | E-GEOD-74547 | biostudies-arrayexpress
Project description:Gene regulatory networks underlying cellular pluripotency are controlled by a core circuitry of transcription factors, including POU5F1 and NANOG in mammals. However, the evolutionary origin and transformation of pluripotency transcriptional networks have not been elucidated in deuterostomes. PR domain-containing protein 14 (PRDM14) is specifically expressed in pluripotent cells and germ cells, and is required for establishing embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice. Here, we compared the functions and expression patterns of PRDM14 orthologues within deuterostomes. Amphioxus PRDM14, zebrafish PRDM14, and the combination of sea urchin PRDM14 and CBFA2T compensated for disruption of the mouse Prdm14 gene in terms of maintaining mouse ESC pluripotency. Interestingly, Prdm14 was expressed in motor neurons, but not in germ cells in amphioxus embryos as observed in zebrafish embryos. Therefore, our results suggest that the integration of the PRDM14–CBFA2T complex into the transcriptional network for pluripotency may be essential for stabilizing pluripotency during the early amniote development.
2019-01-29 | GSE112904 | GEO
Project description:DNA methylation is essential for embryonic development and implicated in the regulation of genomic imprinting. Genomic imprinting is established in the germline through parent-specific methylation of distinct cis-regulatory DNA sequences, called imprinting control regions (ICRs). Which factors bind to the opposing chromatin states at ICRs within the same nuclear environment was not systematically addressed. By using a proximity labelling approach with the methylation sensitive transcription factor ZFP57, we identified ATF7IP and other major components of the epigenetic maintenance machinery at ICRs.
2023-03-10 | PXD034918 | Pride
Project description:To identify the gene changes after PRDM14 knockdown
2010-10-20 | GSE22795 | GEO
Project description:PRDM14 belongs to the PR (PRDI-BF1 and RIZ) domain proteins (PRDM) family which is a subclass of the SET domain proteins, a common domain found in histone modifying enzymes. PRDM14 has been previously implicated to regulate self-renewal of hESCs as knock-down of PRDM14 induced expression of differentiation marker genes and altered the cellular morphology. We showed that PRDM14 directly regulates the expression of key pluripotency gene POU5F1. Genome-wide location profiling experiments revealed that PRDM14 co-localized extensively with other key transcription factors such as OCT4, NANOG and SOX2. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Hence, PRDM14 exemplifies a key transcription factor that is required for the maintenance of human ESC identity and the reacquisition of pluripotency in human somatic cells.
2010-10-20 | GSE22767 | GEO
Project description: Not available
| S-EPMC3847602 | biostudies-literature
Project description: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 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.
2020-07-15 | GSE134666 | GEO
Project description:To identify the gene changes after PRDM14 knockdown 6 samples were collected in total. Each sample is done in triplicate and samples were collected at 3 days after transfection. Luciferase knockdown serves as negative control and PRDM14 knockdown is the experimental sample.
2010-10-20 | E-GEOD-22795 | biostudies-arrayexpress
Project description:Prdm14 is a PR-domain and zinc-finger protein whose expression is restricted to the pluripotent cells of an early embryo, embryonic stem cells (ESCs), and germ cells. Here we show that Prdm14 safeguards mouse ESC maintenance by preventing induction of extraembryonic endoderm (ExEn) fates. Conversely, Prdm14 overexpression impairs ExEn differentiation during embryoid body (EB) formation. Prdm14 occupies and represses genomic loci encoding ExEn differentiation factors, while also binding to and promoting expression of genes associated with ESC self-renewal. Prdm14-bound genomic regions significantly overlap those occupied by Nanog and Oct4, are enriched in a chromatin signature associated with distal regulatory elements, and contain a unique DNA-sequence motif recognized by Prdm14 in vitro. Our work identifies Prdm14 as a new member of mouse ESC (mESC) transcriptional network, which plays a dual role as a context-dependent transcriptional repressor or activator at distal silencers and enhancers.
2010-12-23 | GSE25409 | GEO